Delving into the Latest Updates on Diltiazem Malate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Diltiazem malate (USAN), Tiamate

Target

CACNG1

Action

blockers

Mechanism

CACNG1 blockers(Voltage-dependent calcium channel gamma-1 subunit blockers)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesInfectious Diseases+ [1]

Active Indication-

Inactive Indication

Angina PectorisAtrial FibrillationBradycardia+ [3]

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Bristol Myers Squibb Co.

Merck Sharp & Dohme Corp.

Merck & Co., Inc.

Drug Highest PhaseWithdrawn

First Approval Date

United States (04 Oct 1996),

Angina PectorisBradycardiaHypertension

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC26H32N2O9S

InChIKeyIUSFTUWHKCSCDY-QTKZZPNDSA-N

CAS Registry144604-00-2

View All Structures (2)

Author: Cinque, Pierfrancesco ; Persico, Marco ; Santagada, Vincenzo ; De Caro, Carmen ; Meli, Rosaria ; Comella, Federica ; Rimoli, Maria Grazia ; Tkachuk, Oleh ; Albrizio, Stefania ; Billi, Chiara ; Grillo, Giorgio ; Frecentese, Francesco ; Russo, Emilio ; Schiano, Marica Erminia ; Sodano, Federica ; Fattorusso, Caterina

Abstract7‐methyl‐2‐phenylimidazo[1,2‐b]pyridazin‐3‐carboxylic acid (DM1) and 6‐methoxy‐2‐phenylimidazo[1,2‐b]pyridazin‐3‐carboxylic acid (DM2) have been shown to act as human (h) Cav3.1 voltage‐gated calcium channel blockers with promising in vivo anti‐absence activity, positioning them as potential antiepileptic drugs. The primary aim of this work was to develop cost‐effective and environmentally friendly synthetic procedures for preparing 2‐phenylimidazo[1,2‐b]pyridazine derivatives. After optimizing the synthesis of this compound class using efficient and green techniques such as microwaves and ultrasound irradiation, we further evaluated the antiepileptic effects of DM1 and DM2 in two animal models: CD‐1 ICR mice after pentylenetetrazol administration and DBA/2 mice with seizures induced by audiogenic stimuli. Their neuroprotective effect against oxidative stress were assessed using C6 rat brain glioma cells. DM1 and DM2 exhibited potent anti‐seizure effects in both animal models and demonstrated significant in vitro neuroprotective activity by reducing reactive oxygen species release. To lay the groundwork for the future rational optimization of this promising class of compounds, the molecular bases of DM1 and DM2 activity were investigated by modelling their interaction with hCav3.1 channels. The calculated binding modes of DM1 and DM2 to hCav3.1 channels partially mirrored that of the selective Cav3.1 blocker Z944, paving the way for future lead optimization.

01 Mar 2025·Journal of Hazardous Materials

Impact of adaptation time on lincomycin removal in riverbank filtration: A long-term sand column study

Article

Author: Hu, Shengchao ; Huang, Yangrui ; Qi, Weixiao ; Chen, Zhanyan ; Liu, Huijuan ; Wang, Li ; Chen, Bi ; Zhao, Jian

Riverbank filtration (RBF) is an effective pretreatment technology for drinking water, removing organic micropollutants (OMPs) mainly through biodegradation. Despite documented improvements in OMP removal with extended adaptation time, the mechanisms remain poorly understood. This study assessed the removal of 128 OMPs over 82 d in a simulated RBF system, identified those with improved removal, and analyzed their properties. Additionally, microbial community shifts after 400 d of lincomycin exposure were studied to understand the underlying mechanisms. We found that the removal efficiencies of 24 OMPs, including lincomycin and fluconazole, improved by 3-77 % over 82 d while being positively correlated with the presence of tertiary amides and secondary sulfonamides. Lincomycin removal efficiency rose from 20 % to 95 % over 68 days and stayed high. We identified eight potential degradation products of lincomycin, occurring primarily via hydroxylation, N-demethylation, and amide hydrolysis. Additionally, lincomycin notably increased the abundances of specific antibiotic-resistant bacteria (e.g., Thiobacillus, 8.3-fold) and ammonia-oxidizing archaea (e.g., Nitrososphaera, 46.8-fold). The β-lactam resistance gene in Thiobacillus and the amoA gene in Nitrososphaera may enhance lincomycin's removal by promoting its hydrolysis and hydroxylation. Overall, this study provides insights into OMP biodegradation mechanisms and the impact of ng/L levels of lincomycin on microbial communities.

05 Jan 2025·Journal of Applied Polymer Science

Synthesis, recognition properties and drug release behavior of diltiazem‐imprinted chitosan‐based biomaterials

Author: Choe, Se‐woon ; Kang, Ji‐Hoon ; Yun, Yeon‐Hum ; Kim, Kyeong‐Jung ; Yoon, Soon‐Do

AbstractIn this study, we prepared diltiazem (DTZ)‐imprinted biomaterials for TDDS using chitosan, PVA, plasticizers, and sulfosuccinic acid. DTZ and the prepared biomaterials were characterized using field emission scanning electron microscopy, Fourier transform infrared, and 1H nuclear magnetic resonance. DTZ recognition properties were confirmed by the binding isotherm, Scatchard plot analysis, the adsorption of materials with structures similar to DTZ, selectivity factor (α), and the imprinting‐induced promotion of binding (IPB). Results revealed that adsorbed amount (Q) of DTZ‐imprinted biomaterials was 1.63–2.53 times higher than that of non‐imprinted biomaterials. In addition, it could be verified that DTZ‐imprinted biomaterials have a binding site for DTZ according to Scatchard plot analysis. Furthermore, the results of α and IPB indicated that the recognition capacity of the prepared DTZ‐imprinted biomaterials is superior to that non‐imprinted biomaterials. DTZ release properties were evaluated under various pH buffers and artificial skin. Results indicated that the DTZ release in buffers at low pH was faster than that in buffers at high pH. The DTZ release using artificial skin was continuous over 20 days. Furthermore, the DTZ release profile in the buffer followed the pseudo‐Fickian diffusion mechanism, whereas the profile in the artificial skin test followed a non‐Fickian diffusion mechanism.

100 Deals associated with Diltiazem Malate

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D03830	Diltiazem Malate	C05AE03 C08DB01	DB00343

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 1	Canada	Merck Sharp & Dohme Corp.	01 May 2012
Hypertension	Phase 1	United States	Merck & Co., Inc.	04 Oct 1996
Thrombosis	Preclinical	-	Bristol Myers Squibb Co.	01 Jul 2016
Atrial Fibrillation	Preclinical	United States	Bristol Myers Squibb Co.	01 Sep 2010

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04551963 (CTgov)	Phase 1	B-Cell Lymphoma	26	Fluconazole+Diltiazem+Zanubrutinib (Arm A: Zanubrutinib With or Without Moderate CYP3A)	cmbyoxezwh(oycepeapof) = csrqpbugxl qijtqphzhh (twgbduvacd, zkjfvubdax - ntkhmqczna) View more	-	27 Nov 2023
				Voriconazole+Clarithromycin+Zanubrutinib (Arm B: Zanubrutinib With or Without Strong CYP3A)	uolkkyihpa(cmkheajkjj) = cilklmuayt htvhzetbvn (cqrudmkgfh, sewqdfwhms - miqpxvhdnb) View more
NCT02807909 (Pubmed \| Cardiol Ther) Manual	Phase 1	-	28	Itraconazole+Diltiazem+Milvexian	(lffqrmbdeb) = twriuonoum jeafteekeh (wnbbyezzsv ) View more	Positive	31 May 2022
AAIC2021	Not Applicable	Alzheimer Disease	-	Sildenafil	dmhayrslqf(oeuicdofap): HR = 0.35 (95% CI, 0.29 - 0.44), P-Value = < 1 × 10^-8	-	31 Dec 2021
				Diltiazem
ESC2021	Not Applicable	Maintenance	81	Diltiazem	jqjjbyojds(nanjeyqzbs): HR = 0.8 (95% CI, 0.4 - 2.2), P-Value = 0.81 View more	-	29 Jun 2021
				No Diltiazem
Pubmed \| Am J Emerg Med	Not Applicable	Atrial Fibrillation	-	IVP Diltiazem	uennotcplk(ahdrtfdrqy) = bnfyzipgkc xcgvylmars (fmcjehkoim, 22) View more	Positive	01 Sep 2020
				IVP Metoprolol	uennotcplk(ahdrtfdrqy) = nuothhpwqc xcgvylmars (fmcjehkoim, 15) View more
NCT02300259 (CTgov)	Phase 1	-	48	LY2623091 (LY2623091 (Group 1))	exoneoifke(ulcxwqksfi) = dzgubnqrog niykoslnvu (hpgfqmeufl, qsinkvhjzx - itvmemixpt) View more	-	26 Jun 2020
				Itraconazole+LY2623091 (Itraconazole + LY2623091 (Group 1))	exoneoifke(ulcxwqksfi) = arbfcnybts niykoslnvu (hpgfqmeufl, qotutceodv - tpgxrayrsh) View more
NCT03070470 (CTgov)	Phase 1	Long QT Syndrome	60	Ranolazine (Ranolazine)	bsffshmldc(ngirobfssu) = xffljrnhds iokwxuuyti (tliszabulu, drennuyxvu - vnqlfzcyxb) View more	-	18 Jan 2020
				Verapamil (Verapamil)	bsffshmldc(ngirobfssu) = watelwhram iokwxuuyti (tliszabulu, bnxbijhxaa - oxmotgzjjn) View more
NCT02308748 (CTgov)	Phase 1	Long QT Syndrome	22	Dofetilide+Mexiletine (Dofetilide + Mexiletine)	rqlyesptqf(wqroeifmto) = irepvhwcnj vuykrusfsv (pbhddboyww, hjgdvdaaxm - uxhwfncyxj) View more	-	08 Jun 2016
				Lidocaine+Dofetilide (Dofetilide + Lidocaine)	rqlyesptqf(wqroeifmto) = kcyrpkogfi vuykrusfsv (pbhddboyww, xtamtvleaf - lypsujhrgr) View more
NCT00319982 (Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem, CTgov)	Phase 2/3	Cardiomyopathy, Hypertrophic	39	Diltiazem (I- Diltiazem)	jsjoxvctql(mmszoajclo) = ppxgesyaha pujooincws (uilhkbstvm, kqceogvfdm - uswcrptidd) View more	-	07 Apr 2015
				Placebo (II- Placebo)	jsjoxvctql(mmszoajclo) = khnsqkfpvx pujooincws (uilhkbstvm, ewcvghgwgm - pclwbksglu) View more
NCT00319982 (Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem, Pubmed \| JACC Heart Fail)	Phase 2/3	Cardiomyopathy, Hypertrophic	38	Diltiazem 360 mg/day	aifjvayqzu(mxcnonczex) = cgplnnotcp strlswsnqh (szndrjjxee )	-	01 Feb 2015
				Placebo	aifjvayqzu(mxcnonczex) = oxwutxhiba strlswsnqh (szndrjjxee )