Substituted thiophene fused derivatives, compositions comprising the same and their use as pharmaceuticals

Abstract

There is provided a compound having the Formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug thereof. The compound or pharmaceutically acceptable salt, solvate, or prodrug thereof can be used for the treatment or prevention of a disorder for which an ASICs inhibitor is indicated. There is also provided a use of a compound C having the Formula (I') or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASICs inhibitor is indicated. In some embodiments, the compound Formula (I) or the pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition prepared using compound C is for the treatment or prevention of pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough, or acute lung injury.

Description

Abstract This disclosure provides a compound having formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug thereof. This compound or a pharmaceutically acceptable salt, solvate, or prodrug thereof may be used for the treatment or prevention of diseases for which ASIC inhibitors are applicable. Also provided is the use of compound C having formula (I') or a pharmaceutically acceptable salt, solvate, or prodrug thereof in the preparation of a pharmaceutical composition for the treatment or prevention of diseases for which ASIC inhibitors are applicable. In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition prepared using compound C, is used for the treatment or prevention of pain, arthritis, stroke, epilepsy, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury.

Claims

CLAIMS1. A compound having the Formula (I),or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:Rais -NH2, -NH-OH, -OH, or -NHRb;Rbis C1-C6alkyl, Cs-Cecycloalkyl, or 3- to 6-membered heterocycloalkyl, wherein C1-C6alkyl is optionally substituted with 1 to 3 halogens; represents one of the following residues Aoto A6wherein:R is H or C1-C6alkyl;R' is H or C2-C6alkyl;R1is -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, F, Cl, Br, I, -N(R”)2, C3-C8cycloalkyl,4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, - C(O)R6, or -C(O)OR5, wherein C1-C6alkyl is optionally substituted with 1 to 3 R7substituents and C6-C10aryl is optionally substituted with 1 to 3 R8substituents;R2is C6-C10aryl, unsubstituted C2-C6alkyl, C1-C6alkyl substituted with 1 to 3 R7substituents, C2- Cealkenyl, C2-C6alkynyl, Cl, Br, I, -N(R”)2, Cs-Cecycloalkyl, 4- to 14-membered heterocycloalkyl,5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C6-C10aryl is optionally substituted with 1 to 3 R8substituents, with the proviso that: (i) when Rais -NH2, CKA - - represents residue Ao, R is H, and R1is unsubstituted phenyl, then R2is different thanunsubstituted phenyl; and (ii) when Rais -NH2, represents residue Ao, R is H, and R1is -CN, then R2is different thaneach R” is independently C1-C4alkyl; each R5is independently C1-C6alkyl, wherein each C1-C6alkyl is optionally substituted with 1 to 3 R9substituents; each R6is independently C3-C6cycloalkyl, 4- to 6-membered heterocycloalkyl, or C6-C10aryl, wherein the 4- to 6-membered heterocycloalkyl is optionally substituted with -OH; each R7is independently -OH, -C(O)R11, C3-C5cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1- C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OR20, -SC- i-C6alkyl, -NH2, -NH(C1-C4alkyl), -N(C1-C4alkyl)2, or 4-oxo-1 ,4-dihydro- 1 -pyridinyl, wherein each Cs-Cscycloalkyl is optionally substituted with 1 to 3 R12substituents, each 5- or 6-membered heteroaryl is optionally substituted with 1 to 3 R13substituents, each 4- to 6-membered heterocycloalkyl is optionally substituted with C1-C4alkyl or oxo; each R8is independently halogen, C1-C6alkyl, -OC1-C6alkyl, C3-C6cycloakyl, or 5- to 10- membered heteroaryl, wherein each -OC1-C6alkyl is optionally substituted with -OC1-C4alkyl, and each 5- to 10-membered heteroaryl is optionally substituted with C1-C4alkyl; each R9is independently -OH, -C(O)R15, Cs-Cecycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OC1-C6alkyl, -SC1-C6alkyl, -NH2, -NH(C1- C4alkyl), or -N(C1-C4alkyl)2, wherein each 4- to 6-membered heterocycloalkyl is optionally substituted with C1-C4alkyl, and each -OC1-C6alkyl is optionally substituted with -OC1-C4alkyl; each R11is independently -NH2, -NH(C1-C4alkyl), -N(C1-C4alkyl)2, 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms, or 4- to 6-membered heterocycloalkyl substituted with -OH; each R20is independently C2-C6alkyl or 5- to 10-membered heteroaryl, wherein each C2-C6alkyl is optionally substituted with 1 to 3 R14substituents; each R12is independently C1-C4alkyl, -SC1-C4alkyl, -Ph, -OC1-C4alkyl, -SPh, or-S(O)2Ph, wherein each C1-C4alkyl is optionally substituted with -OH; each R13is independently halogen, C1-C4alkyl, -C(O)OC1-C4alkyl, C3-C6cycloalkyl, -C(O)NH2, - OH, -OC1-C6alkyl, -SC1-C6alkyl, -S(O)2C1-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2,wherein each -OC1-C6alkyl, -SC1-C6alkyl, -S(O)2C1-C6alkyl, -NH(C1-C4alkyl), and -N(C1-C4alkyl)2is optionally substituted with 1 to 3 R9substituents; each R14is independently halogen, -OC1-C4alkyl, or C3-C6cycloalkyl; each R15is independently -NH2, -NH(C1-C4alkyl), -N(C1-C4alkyl)2, or 4- to 6-membered heterocycloalkyl;R4is unsubstituted C2-C6alkyl, C1-C6alkyl substituted with 1 to 3 R9substituents, C3-C8cycloalkyl, C6-C10aryl, 7- to 10-membered partially unsaturated heterocyclic group, or 5- to 10-membered heteroaryl, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R9substituents, and C6- Cioaryl and 5- to 10-membered heteroaryl are optionally substituted with 1 to 3 R10substituents, with the proviso that when Rais -OH,represents residue Ai, and R' is H, then R4is different than -CH2CH3or -C(CH3)3; each R10is independently C1-C4alkyl, halogen, -OC1-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1- C4alkyl)2, wherein each C1-C4alkyl is optionally substituted with 1 to 3 halogens;R2ais unsubstituted C3-C6alkyl, C1-C6alkyl substituted with 1 to 3 R9substituents, C2-C6alkynyl, - NHC(O)OC1-C6alkyl, C3-C8cycloalkyl, or C6-C10aryl, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R9substituents, and C6-C10aryl is optionally substituted with 1 to 3 R22substituents, with the proviso that: (i) when Rais -NH2,represents residue A2, and R is H, then R2ais different than -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CH2OH, -CF3, orC A unsubstituted phenyl; (ii) when Rais -OH, " represents residue A2, and R is H, then R2ais different than -C(CH3)3, -C(CH3)2CH2CH3, -NHC(O)OC(CH3)3, or unsubstituted phenyl; (iii) when Rais -NHCH3or -NHCH2CH3, CZZ represents residue A2, and R is H, then R2ais different than -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl; (iv) when Ra( A is -NHCH(CH3)2, -NHCH2CH2CH3, or -NHcyclopropyl, represents residue A2, and R is H, then R2ais different than -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, or -CF3; and (v) when Rais -NHcyclopentyl or -NHcyclohexyl,represents residue A2, and R is H, then R2ais different than -C(CH3)3or -C(CH3)2CH2CH3; each R22is independently unsubstituted C2-C4alkyl, C1-C4alkyl substituted with 1 to 3 halogens, F, Br, I, -OC3-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2;R1aand R2bare independently -CN, C6-C10aryl, C1-C6alkyl, C3-C8cycloalkyl, -C(O)NH2, - C(O)NHR5, or -C(O)OC1-C6alkyl, wherein each C1-C6alkyl is optionally substituted with 1 to 3 R16substituents and each C6-C10aryl is optionally substituted with 1 to 3 R17substituents; each R16is independently -OH, -C(O)NH2, -C(O)NH(C1-C4alkyl), C3-C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C8alkyl), or -OC1-C4alkyl(OC1-C4alkyl), wherein each C3- C6cycloalkyl is optionally substituted with 1 to 3 R18substituents, each 5- to 10-membered heteroaryl is optionally substituted with 1 to 3 R21substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted with C1-C4alkyl; each R17is independently halogen, C1-C6alkyl, -OC1-C6alkyl, or 5- to 10-membered heteroaryl, wherein each 5- to 10-membered heteroaryl is optionally substituted with C1-C4alkyl; each R18is independently C1-C4alkyl, -SC1-C4alkyl, -Ph, or -OC1-C4alkyl; each R21is independently halogen or C1-C4alkyl;R4ais C1-C6alkyl or C3-C8cycloalkyl, wherein each C1-C6alkyl and C3-C8cycloalkyl are optionally substituted with 1 to 3 R19substituents; each R19is independently halogen, -OH, -OC1-C4alkyl, -SC1-C4alkyl, -NH2, -NH(C1-C4alkyl), or - N(C1-C4alkyl)2;R1band R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from a C3-C8cycloalkyl, a 4- to 14-membered heterocycloalkyl and a 8- to 14-membered partially unsaturated heterocyclic group, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R9substituents, and the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted with oxo, with the proviso that:C A(i) when Rais -NH2,v" represents residue A4, and R is H, then R1band R2cform a cyclic structure different than unsubstituted cyclopentyl, unsubstituted cyclohexyl, or 1 ,3-dioxolane; and(ii) when Rais -NHCH3, -NHCH2CH3, -NHcyclopropyl, -NHCH(CH3)2, or -NHCH2CH2CH3, CZZ represents residue A4, and R is H, then R1band R2cform a cyclic structure different than unsubstituted cyclopentyl;R2dand R4b, together with the carbon atoms to which they are attached, form a C3-C8cycloalkyl or 4- to 14-membered heterocycloalkyl, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R19substituents; andR1cand R3, together with the carbon atoms to which they are attached, form a C3-C8cycloalkyl or 4- to 14-membered heterocycloalkyl, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R19substituents.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R is H.

3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is represented by the formula (la):wherein R1, R2, and Raare as defined in claim 1 and R is as defined in claim 1 or 2.

4. The compound according to claim 3, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1is -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkynyl, F, -N(R”)2, C3-C8cycloalkyl, 5- to 10- membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C1-C8alkyl is optionally substituted with 1 to 3 R7substituents and C6-C10aryl is optionally substituted with 1 to 3 R8substituents;R2is C6-C10aryl, unsubstituted C2-C6alkyl, C1-C6alkyl substituted with 1 to 3 R7substituents, -N(R”)2, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, - C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C6-C10aryl is optionally substituted with 1 to 3 R8substituents, with the proviso that: (i) when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl; and (ii) when Rais -NH2, R is H, andR1is -CN, then R2is different thanR", R5, R6, R7and R8are as defined in claim 1 .

5. The compound according to claim 3 or 4, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1is -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkynyl, F, -N(R”)2, C3-C8cycloalkyl, 5- to 10- membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C1-C6alkylis optionally substituted with 1 to 3 R7substituents and C6-C10aryl is optionally substituted with 1 to 3 R8substituents; andR2is C6-C10aryl, unsubstituted C2-C6alkyl, C1-C6alkyl substituted with 1 to 3 R7substituents, -N(R”)2, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, - C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C6-C10aryl is optionally substituted with 1 to 3 R8substituents, with the proviso that: (i) when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl; and (ii) when Rais -NH2, R is H, andR1is -CN, then R2is different thanand wherein: each R” is C1-C2alkyl; each R5is C1-C6alkyl; each R6is a 4- to 6-membered heterocycloalkyl, or C6-C10aryl, wherein 4- to 6-membered heterocycloalkyl is optionally substituted with -OH; each R7is independently -OH, -C(O)R11, C3-C5cycloalkyl, -CN, C6-C10aryl, halogen, - C(O)OH, 5-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), - N(C1-C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1- C6alkyl), -OR20, -SC1-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2, wherein each C3- C5cycloalkyl is optionally substituted with 1 to 3 R12substituents, each 5-membered heteroaryl is optionally substituted with 1 to 3 R13substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted with C1-C4alkyl or oxo; each R8is independently halogen, C1-C6alkyl, -OC1-C6alkyl or 5- to 10-membered heteroaryl, wherein each 5- to 10-membered heteroaryl is optionally substituted with C1- C4alkyl; each R11is independently -NH2, -NH(C1-C4alkyl), or 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms; each R20is independently C2-C6alkyl or 5- to 10-membered heteroaryl, wherein each C2- C6alkyl is optionally substituted with 1 to 3 R14substituents; each R12is independently C1-C4alkyl, -SC1-C4alkyl, -Ph, -OC1-C4alkyl, -S(O)2Ph or -SPh, wherein each C1-C4alkyl is optionally substituted with -OH; each R13is independently C1-C4alkyl, -C(O)OC1-C4alkyl, C3-C6cycloalkyl, -C(O)NH2or - OH; and each R14is independently halogen or -OC1-C4alkyl.

6. The compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1is -CN, phenyl, C1-C5alkyl, C3alkynyl, F, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C1-C5alkyl is optionally substituted with 1 to 2 R7substituents and phenyl is optionally substituted with 1 R8substituent;R2is phenyl, unsubstituted C2-C4alkyl, C1-C5alkyl substituted with 1 to 2 R7substituents, Cs-Cecycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or - C(O)OR5, wherein phenyl is optionally substituted with 1 R8substituent, with the proviso that when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl; andR5, R6, R7and R8are as defined in claim 1 .

7. The compound according to any one of claims 3 to 6, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1is -CN, phenyl, C1-Csalkyl, C3alkynyl, F, Cs-Cecycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C1-C5alkyl is optionally substituted with 1 to 2 R7substituents and phenyl is optionally substituted with 1 R8substituent; and R2is phenyl, unsubstituted C2-C4alkyl, C1-C5alkyl substituted with 1 to 2 R7substituents, Cs-Cecycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or - C(O)OR5, wherein phenyl is optionally substituted with 1 R8substituent, with the proviso that: (i) when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl; and (ii) when Rais -NH2, R is H, and R1is -CN, then R2is differentand wherein: each R5is C1-C2alkyl; each R6is a 6-membered heterocycloalkyl, or phenyl, wherein 6-membered heterocycloalkyl is optionally substituted with -OH; each R7is independently -OH, -C(O)R11, C3-C5cycloalkyl, -CN, phenyl, F, -C(O)OH, 5- membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC4alkyl), - N(CH2CH3)(C(O)OC4alkyl), 6-membered heterocycloalkyl, -NH(C(O)CH3), -OR20, -NH2, - NHCH2CH3, or -N(Me)2, wherein each Cs-Cscycloalkyl is optionally substituted with 1 to 3 R12substituents, each 5-membered heteroaryl is optionally substituted with 1 to 3 R13substituents, and each 6-membered heterocycloalkyl is optionally substituted with propyl or oxo;each R8is independently -F, -Cl, -Br, -CH3, -OCH3or 5-membered heteroaryl, wherein each 5-membered heteroaryl is optionally substituted with -CH3; each R11is independently -NH2, -NHCH2CH3, or 6-membered heterocycloalkyl containing at least 2 heteroatoms; each R20is independently C2alkyl or 6-membered heteroaryl, wherein each C2alkyl is optionally substituted with 1 R14substituent; each R12is independently C1-C4alkyl, -SCH3, -Ph, -OCH3, -S(O)2Ph or -SPh, wherein Cialkyl is optionally substituted with -OH; each R13is independently C1-C3alkyl, -C(O)OCH2CH3, C3-C4cycloalkyl, -C(O)NH2or -OH; and each R14is independently halogen or -OCH3.

8. The compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R1and R2independently represent R23, or R1represents -F, -ON or -CH3and R2represents R23; wherein R23represents:with the proviso that when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl.

9. The compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R1and R2independently represent R23, or R1represents -CN or -CH3 and R2represents R23; wherein R23represents:with the proviso that when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl.

10. The compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R1and R2independently represent R23, or R1represents -CN or -CH3and R2represents R23; wherein R23represents:with the proviso that when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl.

11. The compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R1and R2independently represent R23, or R1represents -CN or -CH3 and R2represents R23; wherein R23represents:with the proviso that when Rais -NH2, R is H, and R1is unsubstituted phenyl, then R2is different than unsubstituted phenyl.

12. The compound according to any one of claims 3 to 11 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R1and R2are different.

13. The compound according to any one of claims 3 to 12, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R1is -CN.

14. The compound according to any one of claims 3 to 13, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein one of R1and R2is15. The compound according to any one of claims 3 to 14, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein one of R1and R2is16. The compound according to any one of claims 3 to 15, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein one of R1and R2is17. The compound according to claim 1 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is represented by the formula (lb):wherein R4, R’ and Raare as defined in claim 1.

18. The compound according to claim 17, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein R’ is H, with the proviso that when Rais -OH, then R4is different than - CH2CH3 or -C(CH3)3.

19. The compound according to claim 17 or 18, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R4is unsubstituted C2-C6alkyl or C6-C10aryl, with the proviso that when Rais -OH, and R' is H, then R4is different than -CH2CH3or -C(CH3)3.

20. The compound according to any one of claims 17 to 19, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R4is unsubstituted C4alkyl or phenyl, with the proviso that when Rais -OH, and R' is H, then R4is different than -C(CH3)3.

21. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is represented by the formula (Ic):wherein R2aand Raare as defined in claim 1 and R is as defined in claim 1 or 2.

22. The compound according to claim 21 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R2ais unsubstituted C3-C6alkyl, C1-C6alkyl substituted with 1 to 3 R9substituents, C2- Cealkynyl, -NHC(O)OC1-C6alkyl or C6-C10aryl, and wherein each R9is halogen, with the proviso that: (i) when Rais -NH2, and R is H, then R2ais different than - CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl; (ii) when Rais -OH, and R is H, then R2ais different than -C(CH3)3, -C(CH3)2CH2CH3, or unsubstituted phenyl; (iii) when Rais -NHCH3or -NHCH2CH3, and R is H, then R2ais different than -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl; (iv) when Rais -NHCH(CH3)2, -NHCH2CH2CH3, or -NHcyclopropyl, and R is H, then R2ais different than -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, or -CF3; and (v) when Rais -NHcyclopentyl or -NHcyclohexyl, and R is H, then R2ais different than -C(CH3)3or -C(CH3)2CH2CH3.

23. The compound according to claim 21 or 22, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R2ais unsubstituted C3-C5alkyl, C1-C2alkyl substituted with 1 to 3 R9substituents, -CHCH, -NHC(O)OC(CH3)3or phenyl, and wherein each R9is F, with the proviso that: (i) when Rais -NH2, and R is H, then R2ais different than - CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl; (ii) when Rais -OH, and R is H, then R2ais different than -C(CH3)3, -C(CH3)2CH2CH3, or unsubstituted phenyl; (iii) when Rais -NHCH3or -NHCH2CH3, and R is H, then R2ais different than -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl; (iv) when Rais -NHCH(CH3)2, -NHCH2CH2CH3, or -NHcyclopropyl, and R is H, then R2ais different than -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, or -CF3; and (v) when Rais -NHcyclopentyl or -NHcyclohexyl, and R is H, then R2ais different than -C(CH3)3or -C(CH3)2CH2CH3.

24. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is represented by the formula (Id):wherein R1a, R2b, R4aand Raare as defined in claim 1 and R is as defined in claim 1 or 2.

25. The compound according to claim 24, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1aand R2bare independently -CN, C6-C10aryl or C1-C6alkyl; andR4ais C1-C6alkyl.

26. The compound according to claim 24 or 25, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1aand R2bare independently -CN, phenyl or methyl; and R4ais -CH2CH(CH3)2.

27. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is represented by the formula (le):wherein Ra, R1band R2care as defined in claim 1 and R is as defined in claim 1 or 2.

28. The compound according to claim 27, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1band R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from a C3-C8cycloalkyl, a 4- to 14-membered heterocycloalkyl and a 8- to 14-membered partially unsaturated heterocyclic group, wherein the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted with oxo, with the proviso that: (i) when Rais -NH2, and R is H, then R1band R2cform a cyclic structure different than unsubstituted cyclopentyl, unsubstituted cyclohexyl, or 1 ,3-dioxolane; and (ii) when Rais -NHCH3, -NHCH2CH3, -NHcyclopropyl, - NHCH(CH3)2, or -NHCH2CH2CH3, and R is H, then R1band R2cform a cyclic structure different than unsubstituted cyclopentyl.

29. The compound according to claim 27 or 28, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1band R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from a Cs-C / cycloalkyl, a 4- to 14-membered heterocycloalkyl and a 8- to 14-membered partially unsaturated heterocyclic group, wherein the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted with oxo, with the proviso that: (i) when Rais -NH2, and R is H, then R1band R2cform a cyclic structure different than unsubstituted cyclopentyl, unsubstituted cyclohexyl, or 1 ,3-dioxolane; and (ii) when Rais -NHCH3, -NHCH2CH3, -NHcyclopropyl, - NHCH(CH3)2, or -NHCH2CH2CH3, and R is H, then R1band R2cform a cyclic structure different than unsubstituted cyclopentyl.

30. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is represented by the formula (If):wherein Ra, R4band R2dare as defined in claim 1 and R is as defined in claim 1 or 2.

31. The compound according to claim 30, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R2dand R4b, together with the carbon atoms to which they are attached, form a C3- C8cycloalkyl.

32. The compound according to claim 30 or 31 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R2dand R4b, together with the carbon atoms to which they are attached, form a cyclohexane.

33. The compound according to claim 1 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is represented by the formula (Ig):wherein Ra, R1cand R3are as defined in claim 1.

34. The compound according to claim 33, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1cand R3, together with the carbon atoms to which they are attached, form a C3- C8cycloalkyl.

35. The compound according to claim 33 or 34, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:R1cand R3, together with the carbon atoms to which they are attached, form a cyclohexane.

36. The compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein Rais selected from the group consisting of -NH2, -NH- OH, -OH, or -NHRband wherein Rbrepresents:

37. The compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein Rais selected from the group consisting of -NH2, -OH, or -NHRband wherein Rbrepresents:

38. The compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein Rais -NHRband Rbrepresents.

39. The compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein Rais NH2.

40. A compound or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 , 132, 133, 134, 135, 136, 137, 139, 140, 142, 143,144, 145, 146, 147, 148, 149, 150, 151 , 152, 153, 154, 155, 156, 157, 158, 159, 160, 161 , 162,163, 164, 165, 166, 167, 169, 170, 171 , 172, 176, 177, 181 , 182, 183, 186, 187, 188, 189, 190,191 , 192, 194, 195, 198, 223, 224, 227, 228, 229, 230, 231 , 233, 234, 235, 236, 237, 238, 239,240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258,259, 260, 261 , 294, 295, 296, or 297 of Table 1 .

41. The compound according to claim 40, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is Compound 4, 6, 12, 20, 46, 76, 77, 78, 80, 81 , 84, 85, 86, 87, 98, 99, 100, 101 , 105, 109, 120, 121 , 125, 127, 128, 129, 132, 134, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152, 153, 154, 155, 156, 157, 158, 159, 160, 161 ,162, 163, 169, 170, 176, 177, 183, 186, 187, 188, 190, 191 , 192, 195, 198, 223, 229, 235, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 294, 295, or 296 of Table 1.

42. The compound according to claim 40 or 41 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is Compound 6, 98, 120, 127, 128, 129, 137, 143, 144,146, 147, 152, 153, 156, 158, 235, 245, 252, 254, or 255 of Table 1 .

43. The compound according to any one of claims 40 to 42, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is Compound 6, 98, 127, 143, 144, 146,147, 153, 156, 158, or 235 of Table 1 .

44. The compound according to any one of claims 1 to 43, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound is in the form of a racemate or any enantiomer thereof.

45. A pharmaceutical composition comprising: a compound according to any one of claims 1 to 44, or a pharmaceutically acceptable salt, solvate, or prodrug thereof; and a pharmaceutically acceptable carrier, diluent or excipient.

46. Use of a compound C having the Formula (I’):or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASICs inhibitor is indicated, wherein:Rais -NH2, -NH-OH, -OH, or -NHRb;Rbis C1-C6 alkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl, wherein C1-C6alkyl is optionally substituted with 1 to 3 halogens;( A represents one of the following residues Aoto A6wherein:R is H or C1-C6alkyl;R’ is H, C1-C6alkyl or phenyl;R1is -ON, C6-C10aryl, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, F, Cl, Br, I, -N(R”)2, C3-C3cycloalkyl,4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, - C(O)R6, or -C(O)OR5, wherein C1-C6alkyl is optionally substituted with 1 to 3 R7substituents and C6-C10aryl is optionally substituted with 1 to 3 R8substituents;R2is C6-C10aryl, unsubstituted C2-C6alkyl, C1-C6alkyl substituted with 1 to 3 R7substituents, C2- C6alkenyl, C2-C6alkynyl, F, Cl, Br, I, -N(R”)2, C3-C8cycloalkyl, 4- to 14-membered heterocycloalkyl,5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C6-C10aryl is optionally substituted with 1 to 3 R8substituents; with the proviso that when Rais -NH2,represents residue Ao, R is H, and R1is -CN, then R2is different thaneach R” is independently C1-C4alkyl; each R5is independently C1-C6alkyl, wherein each C1-C6alkyl is optionally substituted with 1 to 3 R9substituents; each R6is independently C3-C6cycloalkyl, 4- to 6-membered heterocycloalkyl, or C6-C10aryl, wherein the 4- to 6-membered heterocycloalkyl is optionally substituted with -OH; each R7is independently -OH, -C(O)R11, C3-C5cycloalkyl, -ON, C6-C10aryl, halogen, -C(O)OH, 5 or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1- C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OR20, -SC- i-C6alkyl, -NH2, -NH(C1-C4alkyl), -N(C1-C4alkyl)2, or 4-oxo-1 ,4-dihydro- 1 -pyridinyl, wherein each C3-C5cycloalkyl is optionally substituted with 1 to 3 R12substituents, each 5- or 6-membered heteroaryl is optionally substituted with 1 to 3 R13substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted with C1-C4alkyl or oxo;each R8is independently halogen, C1-C6alkyl, -OC1-C6alkyl, C3-C6cycloakyl, or 5- to 10- membered heteroaryl, wherein each -OC1-C6alkyl is optionally substituted with -OC1-C4alkyl, and each 5- to 10-membered heteroaryl is optionally substituted with C1-C4alkyl; each R9is independently -OH, -C(O)R15, C3-C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OC1-C6alkyl, -SC1-C6alkyl, -NH2, -NH(C1- C4alkyl), or -N(C1-C4alkyl)2, wherein each 4- to 6-membered heterocycloalkyl is optionally substituted with C1-C4alkyl, and each -OC1-C6alkyl is optionally substituted with -OC1-C4alkyl; each R11is independently -NH2, -NH(C1-C4alkyl), -N(C1-C4alkyl)2, 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms, or 4- to 6-membered heterocycloalkyl substituted with -OH; each R20is independently C2-C6alkyl or 5- to 10-membered heteroaryl, wherein each C2-C6alkyl is optionally substituted with 1 to 3 R14substituents; each R12is independently C1-C4alkyl, -SC1-C4alkyl, -Ph, -OC1-C4alkyl, -SPh, or -S(O)2Ph wherein each C1-C4alkyl is optionally substituted with -OH; each R13is independently halogen, C1-C4alkyl, -C(O)OC1-C4alkyl, Cs-Cecycloalkyl, -C(O)NH2, - OH, -OC1-C6alkyl, -SC1-C6alkyl, -S(O)2C1-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2, wherein each -OC1-C6alkyl, -SC1-C6alkyl, -S(O)2C1-C6alkyl, -NH(C1-C4alkyl), and -N(C1-C4alkyl)2is optionally substituted with 1 to 3 R9substituents; each R14is independently halogen, -OC1-C4alkyl, or C3-C6cycloalkyl; each R15is independently -NH2, -NH(C1-C4alkyl), -N(C1-C4alkyl)2, or 4- to 6-membered heterocycloalkyl;R4is C1-C6alkyl, C3-C8cycloalkyl, C6-C10aryl, 7- to 10-membered partially unsaturated heterocyclic group, or 5- to 10-membered heteroaryl, wherein C1-C6alkyl and C3-C8cycloalkyl are optionally substituted with 1 to 3 R9substituents, and C6-C10aryl and 5- to 10-membered heteroaryl are optionally substituted with 1 to 3 R10substituents; each R10is independently C1-C4alkyl, halogen, -OC1-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1- C4alkyl)2, wherein each C1-C4alkyl is optionally substituted with 1 to 3 halogens;R2ais unsubstituted C2-C6alkyl, C1-C6alkyl substituted with 1 to 3 R9substituents, C2-C6alkynyl, - NHC(O)OC1-C6alkyl, C3-C8cycloalkyl, or C6-C10aryl, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R9substituents, and C6-C10aryl is optionally substituted with 1 to 3 R22substituents; each R22is independently C1-C4alkyl, halogen, -OC1-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(Cr C4alkyl)2, wherein each C1-C4alkyl is optionally substituted with 1 to 3 halogens;R1aand R2bare independently -CN, C6-C10aryl, C1-C6alkyl, C3-C8cycloalkyl, -C(O)NH2, - C(O)NHR5, or -C(O)OC1-C6alkyl, wherein each C1-C6alkyl is optionally substituted with 1 to 3 R16substituents and each C6-C10aryl is optionally substituted with 1 to 3 R17substituents; each R16is independently -OH, -C(O)NH2, -C(O)NH(C1-C4alkyl), C3-C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C8alkyl), or -OC1-C4alkyl(OC1-C4alkyl), wherein each C3- C6cycloalkyl is optionally substituted with 1 to 3 R18substituents, each 5- to 10-membered heteroaryl is optionally substituted with 1 to 3 R21substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted with C1-C4alkyl; each R17is independently halogen, C1-C6alkyl, -OC1-C6alkyl, or 5- to 10-membered heteroaryl, wherein each 5- to 10-membered heteroaryl is optionally substituted with C1-C4alkyl; each R18is independently C1-C4alkyl, -SC1-C4alkyl, -Ph, or -OC1-C4alkyl; each R21is independently halogen or C1-C4alkyl;R4ais C1-C6alkyl or C3-C8cycloalkyl, wherein each C1-C6alkyl and C3-C8cycloalkyl are optionally substituted with 1 to 3 R19substituents; each R19is independently halogen, -OH, -OC1-C4alkyl, -SC1-C4alkyl, -NH2, -NH(C1-C4alkyl), or - N(C1-C4alkyl)2;R1band R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from a C3-C8cycloalkyl, a 4- to 14-membered heterocycloalkyl and a 8- to 14-membered partially unsaturated heterocyclic group, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R9substituents, and the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted with oxo; with the proviso thatC A when Rais -NH2, " represents residue A4, and R is H, then R1band R2cform a cyclic structure different than 1 ,3-dioxolane;R2dand R4b, together with the carbon atoms to which they are attached, form a C3-C8cycloalkyl or 4- to 14-membered heterocycloalkyl, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R19substituents; andR1cand R3, together with the carbon atoms to which they are attached, form a C3-C8cycloalkyl or 4- to 14-membered heterocycloalkyl, wherein C3-C8cycloalkyl is optionally substituted with 1 to 3 R19substituents.

47. The use according to claim 46, wherein the compound C is a compound as defined in any one of claims 1 to 44 or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

48. Use of a compound C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASICs inhibitor is indicated, wherein the compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 ,132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149,150, 151 , 152,153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172,176, 177, 181 , 182, 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205,206, 207, 208, 209, 210, 211 , 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228,229, 230, 231 , 233, 234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2.

49. The use according to claim 48, wherein the compound C or the pharmaceutically acceptable salt, solvate, or prodrug thereof is in the form of a racemate or any enantiomer thereof.

50. The use according to any one of claims 46 to 49, wherein the ASICs inhibitor is an ASIC1 a or ASICI b inhibitor.

51. The use according to any one of claims 46 to 50, wherein the ASICs inhibitor is an ASIC1 a inhibitor.

52. The use according to any one of claims 46 to 50, wherein the ASICs inhibitor is an ASIC1 b inhibitor.

53. Use of a compound C as defined in claim 46, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post- traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer’s disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury.

54. The use according to claim 53, wherein the compound C is a compound as defined in any one of claims 1 to 44 or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

55. Use of a compound C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder(PTSD), depression, multiple sclerosis, Alzheimer’s disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury, wherein the compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128,129, 131 , 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150,151 , 152, 153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170,171 , 172, 176, 177, 181 , 182, 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203,204, 205, 206, 207, 208, 209, 210, 211 , 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231 , 233, 234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2.

56. The use according to claim 55, wherein the compound C is Compound 4, 6, 12, 16, 20,24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 , 132,133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152, 153,154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172, 176,177, 181 , 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205, 206, 207,208, 209, 210, 211 , 212, 213, 214, 215, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231 ,233, 234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

57. The use according to claim 55 or 56, wherein the compound C is Compound 4, 6, 12, 16,20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 ,132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152,153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172,176, 177, 181 , 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205, 207,208, 209, 210, 211 , 212, 213, 217, 219, 220, 223, 224, 227, 228, 229, 230, 231 , 233, 234, 235,236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254,255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

58. The use according to any one of claims 55 to 57, wherein the compound C is Compound 6, 76, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161 , 198,220, 235, 245, 247, 252, 254, 255, 257, or 258 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

59. The use according to any one of claims 55 to 58, wherein the compound C is Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158, 220, or 235 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

60. The use according to any one of claims 55 to 59, wherein the compound C or the pharmaceutically acceptable salt, solvate, or prodrug thereof is in the form of a racemate or any enantiomer thereof.

61. The use according to any one of claims 46 to 60, wherein the disorder is pain.

62. The use according to any one of claims 46 to 61 , wherein the disorder is inflammatory pain or neuropathic pain.

63. The use according to any one of claims 46 to 61 , wherein the disorder is inflammatory pain.

64. The use according to any one of claims 46 to 61 , wherein the disorder is neuropathic pain.

65. A method for treating or preventing a disorder for which an ASICs inhibitor is indicated comprising administering to a patient in need thereof a compound C as defined in claim 46, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

66. The method according to claim 65, wherein the compound C is a compound as defined in any one of claims 1 to 44 or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

67. A method for treating or preventing a disorder for which an ASICs inhibitor is indicated comprising administering to a patient in need thereof a compound C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129,131 , 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 ,152, 153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 ,172, 176, 177, 181 , 182, 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204,205, 206, 207, 208, 209, 210, 211 , 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227,228, 229, 230, 231 , 233, 234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2.

68. The method according to claim 67, wherein the compound C or the pharmaceutically acceptable salt, solvate, or prodrug thereof is in the form of a racemate or any enantiomer thereof.

69. The method according to any one of claims 65 to 68, wherein the ASICs inhibitor is an ASICIa or ASICI b inhibitor.

70. The method according to any one of claims 65 to 69, wherein the ASICs inhibitor is an ASICIa inhibitor.

71. The method according to any one of claims 65 to 69, wherein the ASICs inhibitor is an ASICIb inhibitor.

72. A method for treating or preventing a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer’s disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury, comprising administering to a patient in need thereof a compound C as defined in claim 46, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

73. The method according to claim 72, wherein the compound C is a compound as defined in any one of claims 1 to 44 or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

74. A method for treating or preventing a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer’s disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury, comprising administering to a patient in need thereof a compound C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129,131 , 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 ,152, 153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 ,172, 176, 177, 181 , 182, 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204,205, 206, 207, 208, 209, 210, 211 , 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227,228, 229, 230, 231 , 233, 234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247,248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2.

75. The method according to claim 74, wherein the compound C is Compound 4, 6, 12, 16,20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 ,132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152,153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172,176, 177, 181 , 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205, 206,207, 208, 209, 210, 211 , 212, 213, 214, 215, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230,231 , 233, 234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250,251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

76. The method according to claim 74 or 75, wherein the compound C is Compound 4, 6, 12,16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100,101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129,131 , 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 ,152, 153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 ,172, 176, 177, 181 , 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205,207, 208, 209, 210, 211 , 212, 213, 217, 219, 220, 223, 224, 227, 228, 229, 230, 231 , 233, 234,235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253,254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

77. The method according to any one of claims 74 to 76, wherein the compound C is Compound 6, 76, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161 , 198, 220, 235, 245, 247, 252, 254, 255, 257, or 258 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

78. The method according to any one of claims 74 to 77, wherein the compound C is Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158, 220, or 235 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

79. The method according to any one of claims 74 to 78, wherein the compound C or the pharmaceutically acceptable salt, solvate, or prodrug thereof is in the form of a racemate or any enantiomer thereof.

80. The method according to any one of claims 65 to 79, wherein the disorder is pain.

81. The method according to any one of claims 65 to 80, wherein the disorder is inflammatory pain or neuropathic pain.

82. The method according to any one of claims 65 to 80, wherein the disorder is inflammatory pain.

83. The method according to any one of claims 65 to 80, wherein the disorder is neuropathic pain.

84. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for use in the treatment or prevention of a disorder for which an ASICs inhibitor is indicated, wherein the compound is a compound C as defined in claim 46.

85. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to claim 84, wherein the compound C is a compound as defined in any one of claims 1 to 44.

86. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for use in the treatment or prevention of a disorder for which an ASICs inhibitor is indicated, wherein the compound is a compound C being Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 , 132, 133, 134, 135, 136, 137, 139,140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152, 153, 154, 155, 156, 157, 158, 159,160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172, 176, 177, 181 , 182, 183, 186, 187,188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211 , 212,213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231 , 233, 234, 235, 236,237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255,256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2.

87. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to claim 86, wherein the compound C is in the form of a racemate or any enantiomer thereof.

88. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof, for use according to any one of claims 84 to 87, wherein the ASICs inhibitor is an ASIC1 a or ASIC1 b inhibitor.

89. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof, for use according to any one of claims 84 to 88, wherein the ASICs inhibitor is an ASIC1 a inhibitor.

90. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof, for use according to any one of claims 84 to 88, wherein the ASICs inhibitor is an ASIC1 b inhibitor.

91. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for use in the treatment or prevention of a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer’s disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury, wherein the compound is a compound C as defined in claim 46.

92. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to claim 91 , wherein the compound C is a compound as defined in any one of claims 1 to 44.

93. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for use in the treatment or prevention of a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer’s disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury, wherein the compound is a compound C being a Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 , 132, 133, 134, 135,136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152, 153, 154, 155, 156,157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172, 176, 177, 181 , 182,183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209,210, 211 , 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231 , 233,234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2.

94. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to claim 93, wherein the compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81 , 82, 83, 84,85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 , 132, 133, 134, 135,136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152, 153, 154, 155, 156,157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172, 176, 177, 181 , 183,186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210,211 , 212, 213, 214, 215, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231 , 233, 234, 235,236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254,255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 2.

95. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to claim 93 or 94, wherein the compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101 , 105, 106, 109, 113, 114, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 131 , 132, 133,134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152, 153, 154,155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 169, 170, 171 , 172, 176, 177,181 , 183, 186, 187, 188, 189, 190, 191 , 192, 194, 195, 198, 200, 203, 204, 205, 207, 208, 209,210, 211 , 212, 213, 217, 219, 220, 223, 224, 227, 228, 229, 230, 231 , 233, 234, 235, 236, 237, 238, 239, 240, 241 , 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 , 294, 295, 296, or 297 of Table 296. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to any one of claims 93 to 95, wherein the compound C is Compound 6, 76, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161 , 198, 220, 235, 245, 247, 252, 254, 255, 257, or 258 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

97. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to any one of claims 93 to 96, wherein the compound C is Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158, 220, or 235 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

98. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to any one of claims 93 to 97, wherein the compound C is in the form of a racemate or any enantiomer thereof.

99. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to any one of claims 84 to 98, wherein the disorder is pain.

100. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to any one of claims 84 to 99, wherein the disorder is inflammatory pain or neuropathic pain.

101. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to any one of claims 84 to 99, wherein the disorder is inflammatory pain.

102. The compound, or the pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to any one of claims 84 to 99, wherein the disorder is neuropathic pain.