pde1c

PDE5-IN-9对Phosphodiesterase PDE1c 具有抑制作用，可用来治疗高血压、心力衰竭、心肌梗塞、肾衰竭、哮喘、支气管炎和痴呆。

PF-04822163 是一种强效的 PDE1 抑制剂，其 IC50 值为 0.0024 μM。

ITI-214 是一种中枢神经系统活性抑制剂，具有口服生物活性的PDE1抑制剂 (Kiof 58 pM)，对其他 PDE 家族成员和一系列酶、受体、转运体和离子通道具有良好的选择性，在各种运动和认知功能的动物模型中显示出有效性。

PDE1-IN-9 (Compound 7a) 为磷酸二酯酶 1 (PDE1) 的选择性抑制剂，其可抑制PDE1C，IC50为11 nM。PDE1-IN-9 能降低IL-1β、IL-6、TNF-α 和 iNOS的mRNA表达，并抑制一氧化氮 (NO) 和活性氧 (ROS) 的产生。此外，该化合物在大鼠肝微粒体中显示出良好的代谢稳定性。

PDE1-IN-8 (Compound 3f) 是一种 PDE1 抑制剂，其 IC50 为 11 nM。PDE1-IN-8 抑制 cAMP 和 cGMP 信号通路，阻断细胞向肌成纤维细胞的分化和增殖，并在 Bleomycin 诱导的大鼠肺纤维化模型中展现出抗纤维化效果。

PDE1-IN-4 是有效的、选择性的 PDE1 (磷酸二酯酶 -1) 抑制剂，能够作用于 PDE1C (IC50: 10 nM)、PDE1A (IC50: 145 nM) 和 PDE1B (IC50: 354 nM)。PDE1-IN-4 能够调控 cAMP (3′,5′- 环磷酸腺苷) 和 cGMP (3′,5′- 环磷酸鸟苷)，表现出抗纤维化效果。PDE1-IN-4 能够抑制 TGF-β1 诱导的人肺成纤维细胞分化。PDE1-IN-4 能够用于研究特发性肺纤维化 (IPF)。

ITI-214 free base is a picomolar PDE1 inhibitor with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters, and ion channels, exhibits potent PDE1 inhibitory activity (Ki = 58 pM).

PDE1-IN-2 is an PDE1 inhibitor(PDE1C, PDE1B and PDE1A with IC50 values of 6, 140 and 164 nM, respectvely).

Sch59498 is a potent phosphodiesterase 1c (Pde1c) inhibitor.

PF-04449613 is a phosphodiesterase 9A (PDE9A) inhibitor (IC50= 22 nM).1It is selective for PDE9A over PDE1C (IC50= >1,000 nM), as well as over a variety of other PDEs, inhibiting PDE2-8, -10, and -11 activity by less than 30% in a panel of enzymes, ion channels, and transporters at 1 μM but does inhibit the human dopamine transporter (DAT; Ki= 293 nM). PF-04449613 (0.1-100 mg kg, s.c.) increases cerebrospinal fluid (CSF) levels of cyclic GMP (cGMP) in rats. Subcutaneous administration of PF-04449613 (10 mg kg) increases the rate of dendritic spine formation and elimination in mouse primary motor cortex pyramidal neuronsin vivo.2It increases the average running speed of mice in an accelerating rotarod task, indicating improved motor learning, at the same dose. 1.Claffey, M.M., Helal, C.J., Verhoest, P.R., et al.Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitorsJ. Med. Chem.55(21)9055-9068(2012) 2.Lai, B., Li, M., Hu, A., et al.The phosphodiesterase 9 inhibitor PF-04449613 promotes dendritic spine formation and performance improvement after motor learningDev. Neurobiol.78(9)859-872(2018)

DSR-141562 is a new compound that can be taken orally and has a specific ability to inhibit phosphodiesterase 1 (PDE1) in the brain. This compound exhibits a preference for inhibiting human PDE1B, with an IC50 value of 43.9 nM. It also shows moderate inhibition of human PDE1A (IC50 = 97.6 nM) and PDE1C (IC50 = 431.8 nM). DSR-141562 is particularly useful in the study of positive symptoms, negative symptoms, and cognitive impairments associated with schizophrenia.

Tovinontrine (IMR-687) 是一种针对镰状细胞病治疗设计的强效且选择性的磷酸二酯酶-9 (PDE9) 抑制剂。其展现出高效能，对PDE9A1和PDE9A2的IC 50 值分别为8.19 nM和9.99 nM [1]。

PDE1-IN-5 (Compound 10c) 是一种PDE1C选择性抑制剂，IC50为15 nM。该化合物显示出抗炎活性，能够抑制LPS诱导的iNOS、TNF-α、IL-1α、IL-1β和IL-6表达。在DSS诱导的结肠炎小鼠模型中，PDE1-IN-5对抗炎性肠病(IBD)表现出治疗潜力，并可用于IBD相关研究。

Osoresnontrine (BI-409306) 是选择性的PDE9A 抑制剂，IC50=52 nM，对其他 PDE 的活性较弱。它可用于中枢神经系统障碍疾病中提高记忆力的研究。