In this work a theoretical study related to exploring and establishing the relationship between geometry, electronic structure, and various physical properties were determined for two substituted phenylalanine derivatives as tryptophan hydroxylase (TPH) inhibitors; 2-Amino-3-(4-(5-(Naphthalen-2- Ylmethyl-amino) Pyrazin-2-Yl) Phenyl) Propionic Acid and -2-Amino-3-(4-{5-[(Quinolin-3-Ylmethyl)-Amino]- Pyrazin-2-Yl} Phenyl) Propionic Acid, which differ structurally, that carbon atom of naphthalene in compound 1 is replaced by nitrogen atom to form quinine in compound 2. Molecular properties such as high occupied molecular orbital energy (EHOMO), low unoccupied molecular orbital energy (ELUMO), the energy gap between HOMO and LUMO (∆E) and Physical properties, such as electronegativity (x), softness (s), hardness (η), chemical potential (μ), and electrophilicity index (ω), were studied to compare properties of these two compounds in relation to their molecular structure. Results show that the (∆E) values of compound 2 were reduced by the replacement of the hydrogen atom in compound 1 by nitrogen atom in compound 2. Consequently, the stability of compound 2 decreased and its activity increased. Additionally, compound 2 exhibited a high electronic chemical potential value and a low chemical hardness value indicating high levels of polarizability.