Continuous administration of a 14-amino acid peptide YY (PYY) analog, Ac-[d-Pro²⁴,Pya(4)²⁶,Cha^27,36,Aib^28,31,Lys³⁰]PYY(23–36) (4), which has a high binding affinity and agonist activity for the neuropeptide Y2 receptor (Y2R), has previously shown an antiobesity effect in a 2-week diet-induced obesity (DIO) study in mice. However, there remained a possibility to obtain more potent analogs by further improving its pharmacokinetic profile. A combination of the N-terminal 4-imidazolecarbonyl moiety and three amino acid substitutions, trans-4-hydroxy-d-proline (d-Hyp)²⁴, isovaline (Iva)²⁵, and γ-methylleucine (γMeLeu)²⁸, not only improved the binding affinity of the peptide for Y2R but also increased its anorectic activity in lean mice. In a 2-week DIO study in mice, continuous administration of 4-imidazolecarbonyl-[d-Hyp²⁴,Iva²⁵,Pya(4)²⁶,Cha^27,36,γMeLeu²⁸,Lys³⁰,Aib³¹]PYY(23–36) (31, PYY-1119) at a dose of 0.03 mg/kg/day showed a highly potent antiobesity effect, with more than 10% body weight reduction.

一个14个氨基酸的肽YY（PYY）的模拟的连续给药，AC- [ d -Pro ²⁴，PYA（4）²⁶，查^27,36，Aib取代^28,31，赖氨酸³⁰ ] PYY（23-36）（4）对神经肽Y2受体（Y2R）具有高结合亲和力和激动剂活性，先前在对小鼠进行的为期2周的饮食诱发肥胖症（DIO）研究中显示出抗肥胖作用。但是，仍有可能通过进一步改善其药代动力学特性来获得更有效的类似物。N-末端4-咪唑羰基部分的组合和三个氨基酸取代，反式-4-羟基- d -脯氨酸（d -Hyp）²⁴，异戊酸（Iva）²⁵和γ-甲基亮氨酸（γMeLeu）²⁸，不仅改善了肽对Y2R的结合亲和力，而且还提高了其在瘦小鼠中的厌食活性。在小鼠2周DIO研究中，4- imidazolecarbonyl-连续给药[ ð -Hyp ²⁴，IVA ²⁵，PYA（4）²⁶，查^27,36，γMeLeu ²⁸，赖氨酸³⁰，Aib取代³¹ ] PYY（23- 36）（31，PYY-1119）的剂量为0.03 mg / kg /天，显示出很强的抗肥胖作用，体重减轻了10％以上。