pde4 in 3

PDE4-IN-3 is a newly developed oral compound that acts as a potent inhibitor of the enzyme phosphodiesterase 4 (PDE4), displaying a high affinity for inhibition with an IC50 value of 4.2 nM.

M3 PDE4 modulator-1 (10f) 为多功能化合物，具备M3mAChR拮抗和PDE4抑制作用。于OVA大鼠模型中，M3 PDE4 modulator-1 (10-1000 nM kg；iv) 能降低半胱氨酸嗜酸性粒细胞内流。

1-pentyl-1H-indole-3-carboxylic acid 是一种天然存在的吲哚生物碱类化合物，具有多种生物活性，包括抗炎、镇痛、抗氧化和抗真菌、抗肿瘤活性等；它通过结合体内的各种受体和酶发挥作用，包括血清素受体、大麻素受体、PPARγ受体和PDE4酶。

PDE5-IN-13 (Compound 14b) 抑制磷酸二酯酶 5 (PDE5A) 的IC50为3 nM，用于肺动脉高压研究。与PDE1、PDE2、PDE3、PDE4、PDE7、PDE8、PDE9、PDE10和PDE11相比，PDE5-IN-13 对靶点显示出高选择性，并且具有口服活性。

O-Demethyl apremilast is an active metabolite of the phosphodiesterase 4 (PDE4) inhibitor apremilast .1It inhibits the activity of PDE4 isolated from U937 cells and LPS-induced TNF-α production in isolated human peripheral blood mononuclear cells (PBMCs; IC50s = 8.3 and 5.6 μM, respectively). O-Demethyl apremilast is also an oxidative degradation product of apremilast.2,3 1.Hoffmann, M., Kumar, G., Schafer, P., et al.Disposition, metabolism and mass balance of [14C]apremilast following oral administrationXenobiotica41(12)1063-1075(2011) 2.Lu, Y., Shen, X., Hang, T., et al.Identification and characterization of process-related substances and degradation products in apremilast: Process optimization and degradation pathway elucidationJ. Pharm. Biomed. Anal.14170-78(2017) 3.Bhole, R.P., Naksakhare, S.R., and Bonde, C.G.A stability indicating HPTLC method for apremilast and identification of degradation products using MS MSJ. Pharm. Sci. & Res.11(5)1861-1869(2019)

LEO 39652 is a dual-soft PDE4 inhibitor with IC50s of 1.2 nM, 1.2 nM, 3.0 nM and 3.8 nM for PDE4A, PDE4B, PDE4C and PDE4D, respectively. LEO 39652 also inhibits TNF-α with an IC50 value of 6.0 nM. LEO 39652 is used for topical research of Atopic dermatitis (AD) [1]. LEO 39652 shows unbound in vitro potency when measured as LPS induced TNF-α release in human peripheral blood mononuclear cells (PBMC), incubated in serum free medium. LEO 39652 shows a relatively high binding to human serum albumin[2]. LEO 39652 is inactivated both in blood and liver (dual-soft) while stabled in the skin[1].Pharmacokinetic AnalysisLEO 39652 exhibits total clearance (rats 930, minipigs 200 and monkey 300 mL min kg) and ratio to total AUC (rats 4, minipigs 6 and monkey 6 %) following intravenous administration (rats 0.075, minipigs 0.5 and monkeys 2.0 mg kg)[1]. [1]. Jens Larsen, et al. Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3 H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5- a]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel Dual-Soft PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis. J Med Chem. 2020 Dec 10;63(23):14502-14521.[2]. Stefan Eirefelt

Olprinone (Loprinone) Hydrochloride 是一种有效的磷酸二酯酶(PDE) 3抑制剂，对 PDE1，PDE2，PDE3，PDE4 的IC50分别为 150、100、0.35 和 14 μM。Olprinone Hydrochloride 由于具有正性肌力和血管扩张作用而被用于心力衰竭的研究。Olprinone Hydrochloride 具有抗炎活性。

PDE4-IN-11 is a potent phosphodiesterase isoenzyme 4 (PDE4) inhibitor, exhibiting remarkable bronchodilatory and anti-inflammatory characteristics. It is specifically designed for studying obstructive or inflammatory airway diseases [1] [2] [3].

PDE4B D-IN-3 (example 22) 作为PDE4的高效抑制剂，其针对PDE4B2和PDE4D的IC50值分别达到0.071 nM和0.09 nM。