Figures & data
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Figure 1. (A) Structure of one Kv1.5 α-subunit with six membrane-spanning domains and the intracytoplasmic accessory β-subunits. (B) α and accessory β-subunits co-assemble as tetramers to form the functional channel.
![Figure 1. (A) Structure of one Kv1.5 α-subunit with six membrane-spanning domains and the intracytoplasmic accessory β-subunits. (B) α and accessory β-subunits co-assemble as tetramers to form the functional channel.](/cms/asset/f521bf92-baa6-43e2-ac08-88f6deb0fd8b/ienz_a_2018683_f0001_c.jpg)
Figure 2. Structures of (A) AVE-0118. (B) MK-0448. (C) S-0100176. (D) Amiodarone hydrochloride. (E) Vernakalant hydrochloride.
![Figure 2. Structures of (A) AVE-0118. (B) MK-0448. (C) S-0100176. (D) Amiodarone hydrochloride. (E) Vernakalant hydrochloride.](/cms/asset/2f39fe7b-8b65-40a3-b0d1-a0b1bab8e0c7/ienz_a_2018683_f0002_b.jpg)
Scheme 1. Synthesis of DDO-02001 and DDO-02002. Reagents and conditions: (i) EDCI, DMAP, THF, r.t.; (ii) CF3COOH, DMF, r.t.; (iii) K2CO3, CH3CN, 80 °C, reflux.
![Scheme 1. Synthesis of DDO-02001 and DDO-02002. Reagents and conditions: (i) EDCI, DMAP, THF, r.t.; (ii) CF3COOH, DMF, r.t.; (iii) K2CO3, CH3CN, 80 °C, reflux.](/cms/asset/1911957a-c53b-4f6e-958b-cc0080e0c95a/ienz_a_2018683_sch0001_b.jpg)
Scheme 2. Synthesis of DDO-02003-DDO-02009. Reagents and conditions: (i) piperidin-4-one-hydrochloride, K2CO3, r.t.; (ii) NaB(OAc)3H, anhydrous. ClCH2CH2Cl, r.t.
![Scheme 2. Synthesis of DDO-02003-DDO-02009. Reagents and conditions: (i) piperidin-4-one-hydrochloride, K2CO3, r.t.; (ii) NaB(OAc)3H, anhydrous. ClCH2CH2Cl, r.t.](/cms/asset/679f6257-0515-448b-97d1-175b25266c29/ienz_a_2018683_sch0002_b.jpg)
Table 1. Inhibition activities of DDO-02002-DDO-02009 on Kv1.5 channel
Figure 4. Effect of compound DDO-02005 and dronedarone on (A) atrial fibrillation, (B) atrial ERP and (C) ventricle ERP. Values of *p < 0.05, **p < 0.01 and ***p < 0.001 were considered statistically significant.
![Figure 4. Effect of compound DDO-02005 and dronedarone on (A) atrial fibrillation, (B) atrial ERP and (C) ventricle ERP. Values of *p < 0.05, **p < 0.01 and ***p < 0.001 were considered statistically significant.](/cms/asset/3079c87a-c3e5-42da-9f45-ef97f5ced738/ienz_a_2018683_f0004_c.jpg)
Table 2. Pharmacokinetic parameters regarding lead compound DDO-02005 (mean ± SD, n = 6)