Summary of General PD and PK Features in Groups of Ligands of the Different GPCR Classes and State of Modelling Approaches | ||||||
Receptors | GPCR Class | Compounds | References | General features | Modelling | References |
Neuropeptide Y1 | Class A, (peptide receptor) | Y-973 BIBO3304 [1] BIP3226 [2] Cmpd. 5 [4] Cmpd. 23 [5] BMS 193858 [6] | [50] [66] [66] [66] [67] [69] | Selective antagonists with PK drawbacks like high molecular weight, high Pgp ratio or inappropriate log P | Complete crystal structures of NPY receptors yet not available, but interaction at binding pocket of NPY2R investigated | [48] [65] [67] |
Neuropeptide Y2 | Class A, (peptide receptor) | BII246 JNJ31020028 [7] CYM9691 [8] CYM9624 [9] | [65] [70] [63] [63] | |||
Orexin-1 | Class A (peptide receptor) | SB334867 [13] rac-10 [14] Cmpds. 47-51 [15] [16] Cmpd. 54 [17] Cmps. 24 [18] SB674042 [21] | [89] [90] [91] [91] [79] [92] [94] | Selective antagonists with PK drawbacks like high molecular weight, high Pgp ratio or inappropriate log P; low density of the receptors in brain tissue | Complete crystal structure available for both receptor subtypes | [48] |
Orexin-2 | Class A (peptide receptor) | 2-SORA-DMP [22] TCSOX229 [23] Cmpd [24] Cmpd. 4f [25] Diazaspiro-cmpds. [26] [27] [28] CW4 [30] | [94] [95] [96] [97] [97] [98] [99] | |||
CX3CR1 (Fractalkine receptor) | Class A (chemokine receptor) | AZD8797 [37] FBTTP [41] | [42] [49] | Functional antagonist with high log P and good p.o. efficacy | Modelling with US28; Fractalkine characterized; crystal structure of the receptor incomplete | [48] |
Corticotropin releasing factor | Class B1 (peptide receptor) | CP316311 CP376395 [42] BMS6650553 [52] Phenylaminopyrazinones [44] [45] [46] Dihydropyridinpyrazonones [47] [48] [49] [50] [51] | [119] [59] [122] [123]
[120] [121] | Rather allosteric binding and pharmacokinetic drawbacks | Complete CRFR1 crystal structure available; first studies with CP376395 | [48] [59] [60] |