The binding of calcium to cardiac troponin C (cTnC) enhances the binding of troponin I (cTnI) switch region to the regulatory domain of cTnC (cNTnC) and triggers muscle contraction. Several molecules alter the response of the sarcomere by targeting this interface; virtually all have an aromatic core that binds to the hydrophobic pocket of cNTnC and an aliphatic tail that interacts with the switch region of cTnI. W7 has been extensively studied, and the positively charged tail has been shown to be important for its inhibitory action. Herein we investigate the importance of the aromatic core of W7 by synthesizing compounds that have the core region of calcium activator dfbp-o with various lengths of the same tail (D-series). These compounds all bind more tightly to cNTnC-cTnI chimera (cChimera) than the analogous W-series compounds and show increased calcium sensitivity of force generation and ATPase activity, demonstrating that the cardiovascular system is tightly balanced.