Azelnidipine | CS 905 | CCRIS 8650 | CAS#123524-52-7 | calcium channel blocker

MedKoo Cat#: 326711 | Name: Azelnidipine

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Azelnidipine, also known as CS 905 and CCRIS 8650, is a dihydropyridine calcium channel blocker. It is sold in Japan by Daiichi-Sankyo pharmaceuticals, Inc. Unlike nicardipine, it has a gradual onset and has a long-lasting hypotensive effect, with little increase in heart rate.

Chemical Structure

Azelnidipine

CAS#123524-52-7 (racemate）

Theoretical Analysis

MedKoo Cat#: 326711

Name: Azelnidipine

CAS#: 123524-52-7 (racemate）

Chemical Formula: C33H34N4O6

Exact Mass: 582.2478

Molecular Weight: 582.66

Elemental Analysis: C, 68.03; H, 5.88; N, 9.62; O, 16.48

Price and Availability

Size	Price	Availability
1g	USD 150.00	Ready to ship
2g	USD 250.00	Ready to ship
5g	USD 600.00	2 Weeks

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Related CAS #

722455-09-6 (S isomer) 722455-08-5 (R isomer) 123524-52-7 (racemate）

Synonym

CS 905; CS-905; CS905; CCRIS 8650; CCRIS8650; CCRIS-8650; Azelnidipine; brand name CalBlock.

IUPAC/Chemical Name

3-(1-benzhydrylazetidin-3-yl) 5-isopropyl 2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

InChi Key

ZKFQEACEUNWPMT-UHFFFAOYSA-N

InChi Code

InChI=1S/C33H34N4O6/c1-20(2)42-32(38)27-21(3)35-31(34)29(28(27)24-15-10-16-25(17-24)37(40)41)33(39)43-26-18-36(19-26)30(22-11-6-4-7-12-22)23-13-8-5-9-14-23/h4-17,20,26,28,30,35H,18-19,34H2,1-3H3

SMILES Code

O=C(C1=C(N)NC(C)=C(C(OC(C)C)=O)C1C2=CC=CC([N+]([O-])=O)=C2)OC3CN(C(C4=CC=CC=C4)C5=CC=CC=C5)C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T7C05I18

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Azelnidipine(CS 905; Calblock) is a novel dihydropyridine derivative, a L-type calcium channel blocker, and an antihypertensive.

In vitro activity:

THP-1 cells were incubated in culture medium in the absence or presence of 10 µM azelnidipine for 24 h (Fig. 1A). In the absence of azelnidipine, most floating THP-1 cells adhered to the culture dish after stimulation with PMA. In contrast, in the presence of azelnidipine, the number of attached THP-1 cells decreased. The ratio of floating cells to total cells increased from 0.24 to 0.49 (Fig. 1B). To investigate the dose dependency and time course, 0, 1, 10, or 30 µM of azelnidipine were used for up to 4 days. The most effective concentration to prevent adherence of PMA treated THP-1 cells was 10 µM; besides treatment of 30 µM azelnidipine and 50 ng/mL PMA caused cell deaths (Fig. 1C). Azelnidipine was still effective for THP-1 differentiation into macrophage-like morphology extended incubation. Those cells treated with azelnidipine remained round shaped even on day 4 compared with the cells not treated with azelnidipine that showed astrocytic or spider shape (Fig. 1D). Although stimulation with PMA increased the expressions of Apo E (A), MMP9 (B), and LOX-1 (C) mRNA, incubation with azelnidipine for 48 h decreased these expressions by PMA significantly in THP-1 cells (Fig. 2). Azelnidipine inhibited the increase in the uptake of acetylated LDL by THP-1 cells 48, 72, and 96 h after stimulation with PMA. Azelnidipine also reduced the expression of the adhesion molecules ICAM-1 (Fig. 4A) and LOX-1 (Fig. 4B). To investigate the signaling pathway, phosphorylation of MAP kinases was investigated (Fig. 4C). The activation of p38 and JNK were decreased by azelnidipine treatment. Reference: J Atheroscler Thromb. 2018 Aug 1; 25(8): 690–697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099069/

In vivo activity:

This study was designed to examine the effect of long-acting calcium channel blocker (CCB), Azelnidipine (AZL) on contractile dysfunction, intracellular calcium (Ca2+) cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ). STZ-induced diabetic animals showed stable signs of diabetes, including hyperglycemia, reduced levels of insulin. Also there was a noted increase heart/body weight ratio (H/BW). Diabetic rats treated with AZL showed improvement in these physiological parameters. AZL treatment completely abolished the diabetes-induced abnormalities of PS, TPS and TR90 (Figure 1A-D). The maximal velocities of shortening (+dl/dt) and relengthening (-dl/dt) were significantly reduced by diabetes and AZL treatment restored the diabetes-induced dysfunction (Figure1A and 1B). Furthermore, 12-weeks of AZL treatment significantly ablated intracellular Ca2+ abnormalities in STZ treated diabetic rats. Consistent with its response in cardiomyocyte shortening, AZL treatment improved diabetes induced changes in Ca2+ homeostasis including elevated resting intracellular Ca2+ levels, depressed intracellular Ca2+ rise in response to electrical stimuli and prolonged intracellular Ca2+ decay (Figure 2 A-C). AZL in this study not only improves cardiac contractile function but also offers protection against oxidative stress, apoptosis and ultimately leading diabetic cardiomyopathy. Reference: Cardiovasc Diabetol. 2011 Nov 4;10:97. https://pubmed.ncbi.nlm.nih.gov/22054019/

	Solvent	mg/mL	mM
Solubility
	DMSO	82.0	140.73
	Ethanol	11.0	18.88

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 582.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Komoda H, Shiraki A, Oyama JI, Nishikido T, Node K. Azelnidipine Inhibits the Differentiation and Activation of THP-1 Macrophages through the L-Type Calcium Channel. J Atheroscler Thromb. 2018 Aug 1;25(8):690-697. doi: 10.5551/jat.41798. Epub 2018 Feb 3. PMID: 29398679; PMCID: PMC6099069. 2. Teng T, Ridgley DM, Tsoy A, Sun GY, Askarova S, Lee JC. Azelnidipine Attenuates the Oxidative and NFκB Pathways in Amyloid-β-Stimulated Cerebral Endothelial Cells. ACS Chem Neurosci. 2019 Jan 16;10(1):209-215. doi: 10.1021/acschemneuro.8b00368. Epub 2018 Nov 8. PMID: 30399318; PMCID: PMC8091167. 3. Kurobe H, Matsuoka Y, Hirata Y, Sugasawa N, Maxfield MW, Sata M, Kitagawa T. Azelnidipine suppresses the progression of aortic aneurysm in wild mice model through anti-inflammatory effects. J Thorac Cardiovasc Surg. 2013 Dec;146(6):1501-8. doi: 10.1016/j.jtcvs.2013.02.073. Epub 2013 Mar 25. PMID: 23535154 4. Kain V, Kumar S, Sitasawad SL. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis. Cardiovasc Diabetol. 2011 Nov 4;10:97. doi: 10.1186/1475-2840-10-97. PMID: 22054019; PMCID: PMC3234183.

In vitro protocol:

In vivo protocol:

1. Kurobe H, Matsuoka Y, Hirata Y, Sugasawa N, Maxfield MW, Sata M, Kitagawa T. Azelnidipine suppresses the progression of aortic aneurysm in wild mice model through anti-inflammatory effects. J Thorac Cardiovasc Surg. 2013 Dec;146(6):1501-8. doi: 10.1016/j.jtcvs.2013.02.073. Epub 2013 Mar 25. PMID: 23535154. 2. Kain V, Kumar S, Sitasawad SL. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis. Cardiovasc Diabetol. 2011 Nov 4;10:97. doi: 10.1186/1475-2840-10-97. PMID: 22054019; PMCID: PMC3234183

1: Susa N, Nishida Y, Yada Y, Nakayama T, Asai S, Takahashi Y. Comparative effect of fixed-dose combination tablets of candesartan cilexetil/amlodipine versus olmesartan medoxomil/azelnidipine on laboratory parameters in patients with hypertension: a retrospective cohort study. Clin Exp Hypertens. 2016;38(2):173-9. doi: 10.3109/10641963.2015.1081214. Epub 2015 Oct 9. PubMed PMID: 26453437. 2: Tawaramoto K, Kaneto H, Hashiramoto M, Kawasaki F, Tatsumi F, Shimoda M, Kamei S, Matsuki M, Mune T, Kaku K. Azelnidipine, but not amlodipine, reduces urinary albumin excretion and carotid atherosclerosis in subjects with type 2 diabetes: blood pressure control with olmesartan and azelnidipine in Type 2 diabetes (BOAT2 study). Diabetol Metab Syndr. 2015 Sep 17;7:80. doi: 10.1186/s13098-015-0073-9. eCollection 2015. PubMed PMID: 26388951; PubMed Central PMCID: PMC4574138. 3: Tatsumi F, Kaneto H, Hashiramoto M, Tawaramoto K, Obata A, Kimura T, Shimoda M, Hamamoto S, Kanda-Kimura Y, Kamei S, Mune T, Matsuda M, Kaku K. Anti-hypertensive azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes. Endocr J. 2015;62(8):741-7. doi: 10.1507/endocrj.EJ15-0273. Epub 2015 Jul 13. PubMed PMID: 26073866. 4: Takihata M, Nakamura A, Kondo Y, Kawasaki S, Kimura M, Terauchi Y. Comparison of Azelnidipine and Trichlormethiazide in Japanese Type 2 Diabetic Patients with Hypertension: The COAT Randomized Controlled Trial. PLoS One. 2015 May 4;10(5):e0125519. doi: 10.1371/journal.pone.0125519. eCollection 2015. PubMed PMID: 25938807; PubMed Central PMCID: PMC4418830. 5: Patel JK, Patel NK. Validated Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Azelnidipine and Olmesartan in Their Combined Dosage Form. Sci Pharm. 2014 Feb 27;82(3):541-54. doi: 10.3797/scipharm.1312-14. eCollection 2014 Sep. PubMed PMID: 25853066; PubMed Central PMCID: PMC4318177. 6: Chen BL, Zhang YZ, Luo JQ, Zhang W. Clinical use of azelnidipine in the treatment of hypertension in Chinese patients. Ther Clin Risk Manag. 2015 Feb 24;11:309-18. doi: 10.2147/TCRM.S64288. eCollection 2015. Review. PubMed PMID: 25750535; PubMed Central PMCID: PMC4348133. 7: Yamamoto H, Kawada T, Shimizu S, Kamiya A, Turner MJ, Miyazaki S, Sugimachi M. Acute effects of intravenous nifedipine or azelnidipine on open-loop baroreflex static characteristics in rats. Life Sci. 2015 Apr 1;126:37-41. doi: 10.1016/j.lfs.2015.01.024. Epub 2015 Feb 21. PubMed PMID: 25707754. 8: Gao Y, Li B, Zhu B, Liu D, Zhao H, Fang Z, Wang H, Lou H. A liquid chromatography-tandem mass spectrometric assay for the antihypertensive agent azelnidipine in human plasma with application to clinical pharmacokinetics studies. Biomed Chromatogr. 2015 Jul;29(7):970-4. doi: 10.1002/bmc.3399. Epub 2014 Dec 4. PubMed PMID: 25472837. 9: Shimada K, Miyauchi K, Daida H. Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders. Expert Rev Cardiovasc Ther. 2015 Jan;13(1):23-31. doi: 10.1586/14779072.2015.986464. Epub 2014 Dec 1. Review. PubMed PMID: 25434474. 10: Iwakura K, Ito H, Ishii K, Date M, Nakamura F, Nagano T, Takiuchi S; Clinical impact of Azelnidipine on Left VentricuLar diastolic function and OutComes in patients with hypertension (CALVLOC) trial investigators. Changes in left ventricular relaxation after azelnidipine treatment in hypertensive patients with diabetes: subanalysis of a prospective single-arm multicentre study. BMJ Open. 2014 Sep 30;4(9):e006136. doi: 10.1136/bmjopen-2014-006136. PubMed PMID: 25270860; PubMed Central PMCID: PMC4179422. 11: Zhao J, Ozawa K, Kyotani Y, Nagayama K, Ito S, Komatsubara AT, Tsuji Y, Yoshizumi M. Azelnidipine inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch. PLoS One. 2014 Jul 17;9(7):e102813. doi: 10.1371/journal.pone.0102813. eCollection 2014. PubMed PMID: 25032824; PubMed Central PMCID: PMC4102561. 12: Inomata J, Murai H, Kaneko S, Hamaoka T, Ikeda T, Kobayashi D, Usui S, Furusho H, Sugiyama Y, Takata S, Takamura M. Differential effects of azelnidipine and amlodipine on sympathetic nerve activity in patients with primary hypertension. J Hypertens. 2014 Sep;32(9):1898-904. doi: 10.1097/HJH.0000000000000270. PubMed PMID: 24979307. 13: Omote Y, Deguchi K, Kono S, Liu W, Kurata T, Hishikawa N, Yamashita T, Ikeda Y, Abe K. Synergistic neuroprotective effects of combined treatment with olmesartan plus azelnidipine in stroke-prone spontaneously hypertensive rats. J Neurosci Res. 2014 Oct;92(10):1330-7. doi: 10.1002/jnr.23406. Epub 2014 May 20. PubMed PMID: 24839960. 14: Motoki H, Koyama J, Izawa A, Tomita T, Miyashita Y, Takahashi M, Ikeda U. Impact of azelnidipine and amlodipine on left ventricular mass and longitudinal function in hypertensive patients with left ventricular hypertrophy. Echocardiography. 2014 Nov;31(10):1230-8. doi: 10.1111/echo.12548. Epub 2014 Mar 20. PubMed PMID: 24645985. 15: Miyazaki S, Hamada T, Hirata S, Ohtahara A, Mizuta E, Yamamoto Y, Kuwabara M, Nosaka Y, Igawa O, Ogino K, Kato M, Yoshida A, Ninomiya H, Cheng J, Moriwaki Y, Yamamoto K, Hisatome I. Effects of azelnidipine on uric acid metabolism in patients with essential hypertension. Clin Exp Hypertens. 2014;36(7):447-53. doi: 10.3109/10641963.2013.846359. Epub 2014 Jan 16. PubMed PMID: 24433018. 16: Uzui H, Morishita T, Nakano A, Amaya N, Fukuoka Y, Ishida K, Arakawa K, Lee JD, Tada H. Effects of combination therapy with olmesartan and azelnidipine on serum osteoprotegerin in patients with hypertension. J Cardiovasc Pharmacol Ther. 2014 May;19(3):304-9. doi: 10.1177/1074248413511692. Epub 2013 Nov 28. PubMed PMID: 24288395. 17: Uramatsu T, Nishino T, Obata Y, Sato Y, Furusu A, Koji T, Miyazaki T, Kohno S. Involvement of apoptosis inhibitor of macrophages in a rat hypertension model with nephrosclerosis: possible mechanisms of action of olmesartan and azelnidipine. Biol Pharm Bull. 2013;36(8):1271-7. PubMed PMID: 23902971. 18: Gao G, Liu XC, Jing WB, Yang Q, He GW. Vasorelaxation induced by new third-generation dihydropyridine calcium antagonist azelnidipine in human internal mammary artery. Ann Thorac Surg. 2013 Oct;96(4):1316-21. doi: 10.1016/j.athoracsur.2013.05.020. Epub 2013 Jul 26. PubMed PMID: 23895889. 19: Iribe G, Kaihara K, Ito H, Naruse K. Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes. Eur J Pharmacol. 2013 Sep 5;715(1-3):142-6. doi: 10.1016/j.ejphar.2013.05.030. Epub 2013 Jun 4. PubMed PMID: 23747592. 20: Bahrudin U, Ikeda N, Utami SB, Maharani N, Morikawa K, Li P, Sobirin MA, Hasegawa A, Sakata S, Endo R, Rifqi S, Shirayoshi Y, Yamamoto K, Ninomiya H, Hisatome I. Simultaneous treatment with azelnidipine and olmesartan inhibits apoptosis of Hl-1 cardiac myocytes expressing E334k cMyBPC. Drug Res (Stuttg). 2013 Oct;63(10):515-20. doi: 10.1055/s-0033-1347188. Epub 2013 Jun 5. PubMed PMID: 23740383.