This paper reports the change in equilibrium pressure-temperature (pT) boundaries in a methane (CH4)-water system by adding three pyrazine analogues: 2-methylpyrazine, 2,3-dimethylpyrazine, and 2,3,5-trimethylpyrazine. The 2-methylpyrazine, 2,3-dimethylpyrazine, and 2,3,5-trimethylpyrazine showed no effect on the clathrate hydrate structure that formed in the CH4-water system upon analysis via Raman spectroscopy. Raman spectra revealed that clathrate crystals that formed in the CH4-pyrazine analogue-water system were of a structure-I CH4 hydrate. Phase equilibrium pT boundaries in the three CH4-pyrazine analogue-water systems shifted to a higher p and lower T condition than that for the CH4-water system with no additive. The higher p/lower T shift confirmed that 2-methylpyrazine, 2,3-dimethylpyrazine, and 2,3,5-trimethylpyrazine act as thermodynamic inhibitors for hydrate formation. The order of Delta T, a lower T shift from the CH4-water system, was as follows: 2-methylpyrazine-water > 2,3-dimethylpyrazine > 2,3,5-trimethylpyrazine. This order is in agreement with the number of -CH3 groups in the molecules.