Benzamil

Names
IUPAC name

3,5-diamino-N-[(1E)-amino(benzylamino)methylidene]-6-chloropyrazine-2-carboxamide

Identifiers

CAS Number

* 2898-76-2 Y

3D model (JSmol)

* Interactive image
* Interactive image

ChEMBL |

* ChEMBL212579 Y

ChemSpider |

* 97202 Y

IUPHAR/BPS

* 4145

KEGG |

* C13751 Y

MeSH | benzamil

PubChem CID

* 108107

UNII |

* 04659UUJ94 Y

InChI

* InChI=1S/C13H14ClN7O/c14-9-11(16)20-10(15)8(19-9)12(22)21-13(17)18-6-7-4-2-1-3-5-7/h1-5H,6H2,(H4,15,16,20)(H3,17,18,21,22) Y

Key: KXDROGADUISDGY-UHFFFAOYSA-N Y

* InChI=1/C13H14ClN7O/c14-9-11(16)20-10(15)8(19-9)12(22)21-13(17)18-6-7-4-2-1-3-5-7/h1-5H,6H2,(H4,15,16,20)(H3,17,18,21,22)

Key: KXDROGADUISDGY-UHFFFAOYAA

SMILES

* Clc2nc(C(=O)\N=C(/N)NCc1ccccc1)c(N)nc2N

* Clc2nc(C(=O)NC(=N/Cc1ccccc1)/N)c(nc2N)N

Properties

Chemical formula

| C13H14ClN7O
Molar mass | 319.75 g/mol

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Y verify (what is YN ?)
Infobox references

Tracking categories (test):

* SizeSet

Benzamil or benzyl amiloride is a potent blocker of the ENaC channel[1] and also a sodium-calcium exchange blocker.[2][3] It is a potent analog of amiloride, and is marketed as the hydrochloride salt (benzamil hydrochloride). As amiloride, benzamil has been studied as a possible treatment for cystic fibrosis,[4] although with disappointing results.[5]

## Contents

* 1 Structure
* 2 Mechanism of action
* 3 References
* 4 External links

## Structure

Benzamil is a benzyl group-containing analog of amiloride. Like amiloride, it is a guanidinium group-containing pyrazine derivative.

## Mechanism of action

Amiloride.

Benzamil is closely related to amiloride. By adding the benzyl group to the nitrogen of the guanidinium group the activity is increased several hundredfold.[6]

Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys (this mechanism is the same for triamterene). This promotes the loss of sodium and water from the body, but without depleting potassium.

## References

1. ↑ Chalfant, M.L. (1995). "Regulation of epithelial Na+ channels from M-1 cortical collecting duct cells". American Journal of Physiology. Renal Physiology 271 (4): f861–f870. doi:10.1152/ajprenal.1996.271.4.f861. PMID 8898016.
2. ↑ Gomez-Sanchez, E. P.; Gomez-Sanchez C. E. (September 1995). "Effect of central infusion of benzamil on Dahl S rat hypertension". Am J Physiol 269 (3, pt 2): H1044–7. doi:10.1152/ajpheart.1995.269.3.H1044. PMID 7573500.
3. ↑ Lee, Y. S.; Sayeed, M. M.; Wurster, R. D. (January 6, 1995). "Intracellular Ca2+ mediates the cytotoxicity induced by bepridil and benzamil in human brain tumor cells.". Cancer Letters 88 (1): 87-91. doi:10.1016/0304-3835(94)03619-T. PMID 7850778. http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=54226. Retrieved 2008-05-01.
4. ↑ "The effect of topical benzamil and amiloride on nasal potential difference in cystic fibrosis". Eur. Respir. J. 14 (3): 693–6. September 1999. doi:10.1034/j.1399-3003.1999.14c32.x. PMID 10543294. http://erj.ersjournals.com/cgi/pmidlookup?view=long&pmid=10543294.
5. ↑ "Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease". J. Pharmacol. Exp. Ther. 311 (3): 929–38. December 2004. doi:10.1124/jpet.104.071886. PMID 15273255. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15273255.
6. ↑ Kleyman, T. R.; Cragoe E. J. Jr. (October 1988). "Amiloride and its analogs as tools in the study of ion transport". J Membr Biol 105 (1): 1-21. doi:10.1007/BF01871102. PMID 2852254.

## External links

* v
* t
* e

Ion channel modulators

Calcium|

| VDCCs|

| Blockers|

* L-type-selective: Dihydropyridines: Amlodipine
* Aranidipine
* Azelnidipine
* Barnidipine
* Clevidipine
* Cronidipine
* Darodipine
* Dexniguldipine
* Elgodipine
* Elnadipine
* Felodipine
* Flordipine
* Furnidipine
* Iganidipine
* Isradipine
* Lacidipine
* Lemildipine
* Lercanidipine
* Levamlodipine
* Levniguldipine
* Manidipine
* Mepirodipine
* Mesudipine
* Nicardipine
* Nifedipine
* Niguldipine
* Niludipine
* Nilvadipine
* Nimodipine
* Nisoldipine
* Nitrendipine
* Olradipine
* Oxodipine
* Palonidipine
* Pranidipine
* Ryodipine (riodipine)
* Sagandipine
* Sornidipine
* Teludipine
* Tiamdipine
* Trombodipine
* Vatanidipine; Diltiazem derivatives: Clentiazem
* Diltiazem
* Iprotiazem
* Nictiazem
* Siratiazem; Phenylalkylamines: Anipamil
* Dagapamil
* Devapamil
* Dexverapamil
* Emopamil
* Etripamil
* Falipamil
* Gallopamil
* Levemopamil
* Nexopamil
* Norverapamil
* Ronipamil
* Tiapamil
* Verapamil; Others: AH-1058
* Brinazarone
* Budiodarone
* Celivarone
* Cyproheptadine
* Dronedarone
* Fantofarone
* SR-33805
* Tetrahydropalmatine

* N-type-selective: ω-Conotoxins
* ω-Conotoxin GVIA
* Caroverine
* Huwentoxin XVI
* Leconotide (ω-conotoxin CVID)
* PD-173212
* Ralfinamide
* Safinamide
* Z160
* Ziconotide (ω-conotoxin MVIIA)

* P-type-selective: ω-Agatoxin IVA
* ω-Agatoxin IVB

* R-type-selective: SNX-482

* T-type-selective: ABT-639
* ML-218
* Niflumic acid
* NNC 55-0396
* ProTx I
* Z944
* Zonisamide

* Non-selective: ω-Agatoxin TK
* ω-Conotoxin MVIIC
* Benidipine
* Bepridil
* Cilnidipine
* Cinnarizine
* Dotarizine
* Efonidipine
* Flunarizine
* Lamotrigine
* Levetiracetam
* Lomerizine
* Loperamide
* Mibefradil
* NP078585
* Ruthenium red
* TROX-1

* α2δ subunit-selective (gabapentinoids): 4-Methylpregabalin
* Arbaclofen
* Arbaclofen placarbil
* Atagabalin
* Baclofen
* Gabapentin
* Gabapentin enacarbil
* Imagabalin
* Mirogabalin
* PD-200,347
* PD-217,014
* PD-299,685
* Phenibut
* Pregabalin

* Others/unsorted: Bencyclane
* Berbamine
* Bevantolol
* Canadine
* Carboxyamidotriazole
* Cycleanine
* Dauricine
* Dimeditiapramine
* Diproteverine
* Enpiperate
* Eperisone
* Elpetrigine
* Ethadione
* Ethanol (alcohol)
* Ethosuximide
* Fasudil
* Fendiline
* Fostedil
* Imepitoin
* JTV-519
* Lidoflazine
* Magnesium
* Manoalide
* Mesuximide
* Monatepil
* Naftopidil
* Ochratoxin A
* Osthol
* Otilonium bromide
* Paramethadione
* Phensuximide
* Pinaverium bromide
* Prenylamine
* Rhynchophylline
* Sesamodil
* Silperisone
* Sipatrigine
* Terodiline
* Tetrandrine
* Tolperisone
* Trimethadione
* Valperinol

|

Activators|

* L-type-selective: Bay K8644

Potassium|

| VGKCs|

| Blockers|

* 3,4-Diaminopyridine (amifampridine)
* 4-Aminopyridine (fampridine/dalfampridine)
* Adekalant
* Almokalant
* Amiodarone
* Azimilide
* Bretylium
* Bunaftine
* Charybdotoxin
* Clamikalant
* Conotoxins
* Dalazatide
* Dendrotoxin
* Dofetilide
* Dronedarone
* E-4031
* Hanatoxin
* HgeTx1
* HsTx1
* Ibutilide
* Inakalant
* Kaliotoxin
* Linopirdine
* Lolitrem B
* Maurotoxin
* Nifekalant
* Notoxin
* Paxilline
* Pinokalant
* Quinidine
* ShK-186
* Sotalol
* Tedisamil
* Terikalant
* Tetraethylammonium
* Vernakalant

* hERG (KCNH2, Kv11.1)-specific: Ajmaline
* Amiodarone
* AmmTX3
* Astemizole
* Azaspiracid
* AZD1305
* Azimilide
* Bedaquiline
* BeKm-1
* BmTx3
* BRL-32872
* Chlorpromazine
* Cisapride
* Clarithromycin
* Darifenacin
* Dextropropoxyphene
* Diallyl trisulfide
* Domperidone
* E-4031
* Ergtoxins
* Erythromycin
* Gigactonine
* Haloperidol
* Ketoconazole
* Norpropoxyphene
* Orphenadrine
* Pimozide
* PNU-282,987
* Promethazine
* Quinidine
* Ranolazine
* Roxithromycin
* Sertindole
* Solifenacin
* Tamulotoxin
* Terodiline
* Terfenadine
* Thioridazine
* Tolterodine
* Vanoxerine
* Vernakalant

* KCNQ (Kv7)-specific: Linopirdine
* XE-991
* Spooky toxin (SsTx)

|

Activators|

* KCNQ (Kv7)-specific: Flupirtine
* Retigabine

IRKs|

| Blockers|

* KATP-specific: Acetohexamide
* Carbutamide
* Chlorpropamide
* Glibenclamide (glyburide)
* Glibornuride
* Glicaramide
* Gliclazide
* Glimepiride
* Glipizide
* Gliquidone
* Glisoxepide
* Glyclopyramide
* Glycyclamide
* Metahexamide
* Mitiglinide
* Nateglinide
* Repaglinide
* Tolazamide
* Tolbutamide

* GIRK-specific: Barium
* Caramiphen
* Cloperastine
* Clozapine
* Dextromethorphan
* Ethosuximide
* Ifenprodil
* Tertiapin
* Tipepidine

|

Activators|

* KATP-specific: Aprikalim
* Bimakalim
* Cromakalim
* Diazoxide
* Emakalim
* Levcromakalim
* Mazokalim
* Minoxidil
* Naminidil
* Nicorandil
* Pinacidil
* Rilmakalim
* Sarakalim

* GIRK-specific: ML-297 (VU0456810)

KCa|

| Blockers|

* BKCa-specific: Ethanol (alcohol)
* GAL-021

|

Activators|

* BKCa-specific: Flufenamic acid
* Meclofenamic acid
* Niflumic acid
* Nimesulide
* Rottlerin (mallotoxin)
* Tolfenamic acid

K2Ps|

| Blockers|

* 12-O-Tetradecanoylphorbol-13-acetate
* Arachidonic acid
* Fluoxetine
* Norfluoxetine

|

Activators|

* Riluzole

Sodium|

| VGSCs|

| Blockers|

* Antianginals: Ranolazine

* Antiarrhythmics (class I): Ajmaline
* Aprindine
* Disopyramide
* Dronedarone
* Encainide
* Flecainide
* Lidocaine
* Lorajmine
* Lorcainide
* Mexiletine
* Moricizine
* Pilsicainide
* Prajmaline
* Procainamide
* Propafenone
* Quinidine
* Sparteine
* Tocainide

* Anticonvulsants: Acetylpheneturide
* Carbamazepine
* Cenobamate
* Chlorphenacemide
* Elpetrigine
* Eslicarbazepine acetate
* Ethotoin
* Fosphenytoin
* Lacosamide
* Licarbazepine
* Mephenytoin
* Oxcarbazepine
* Oxitriptyline
* Phenacemide
* Pheneturide
* Phenytoin
* Rufinamide
* Sipatrigine
* Topiramate
* Sodium valproate
* Valnoctamide
* Valproate pivoxil
* Valproate semisodium
* Valproic acid
* Valpromide
* Zonisamide

* Local anesthetics: pFBT
* Amylocaine
* Articaine
* Benzocaine
* Bupivacaine (Levobupivacaine, Ropivacaine)
* Butacaine
* Butamben
* Chloroprocaine
* Cinchocaine
* Cocaine
* Cyclomethycaine
* Dimethocaine
* Diphenhydramine
* Etidocaine
* Hexylcaine
* Iontocaine
* Lidocaine
* Mepivacaine
* Meprylcaine
* Metabutoxycaine
* Orthocaine
* Piperocaine
* Prilocaine
* Procaine
* Propoxycaine
* Proxymetacaine
* Risocaine
* Tetracaine
* Trimecaine

* Analgesics: AZD-3161
* DSP-2230
* Funapide
* GDC-0276
* NKTR-171
* PF-04531083
* PF-05089771
* Ralfinamide
* Raxatrigine
* RG7893 (GDC-0287)

* Toxins: Conotoxins
* Neosaxitoxin
* Saxitoxin
* Tetrodotoxin
* Zetekitoxin AB

* Others: Buprenorphine
* Evenamide
* Menthol (mint)
* Safinamide
* Tricyclic antidepressants

|

Activators|

* Aconitine
* Atracotoxins (ω-Atracotoxin, Robustoxin, Versutoxin)
* Batrachotoxin
* Ciguatoxins
* Grayanotoxins
* Poneratoxin

ENaC|

| Blockers|

* Amiloride
* Benzamil
* Triamterene

|

Activators|

* Solnatide

ASICs|

| Blockers|

* A-317567
* Amiloride
* Aspirin
* Ibuprofen
* PcTX1

|

Chloride|

| CaCCs|

| Blockers|

* Crofelemer
* DIDS
* Ethacrynic acid
* Flufenamic acid
* Fluoxetine
* Furosemide
* Glibenclamide
* Mefloquine
* Mibefradil
* Niflumic acid

|

Activators|

* Carbachol

CFTR|

| Blockers|

* Glibenclamide
* Lonidamine
* Piretanide

|

Activators|

* 1,7-Phenanthroline
* 1,10-Phenanthroline
* 4,7-Phenanthroline
* 7,8-Benzoquinoline
* Ivacaftor
* Phenanthridine

Unsorted|

| Blockers|

* Bumetanide
* Flufenamic acid
* Meclofenamic acid
* Mefenamic acid
* Mepacrine
* Niflumic acid
* Talniflumate
* Tolfenamic acid
* Trifluoperazine

|

Others|

| TRPs|

* See here instead.

|

LGICs|

* See here instead.

See also: Receptor/signaling modulators • Transient receptor potential channel modulators

* v
* t
* e

Antihypertensives: diuretics (C03)

Sulfonamides
(and etacrynic acid)|

| CA inhibitors (at PT)|

* Acetazolamide

|

Loop (Na-K-Cl at AL)|

* Furosemide#
* Azosemide
* Bumetanide
* Etacrynic acid
* Etozolin
* Muzolimine
* Ozolinone
* Piretanide
* Tienilic acid
* Torasemide

[[Chemistry:ThiThiazides (Sodium-chloride Na-Cl at Distal convoluted tubule|DCT]],
Calcium-sparing)|

* Altizide
* Bendroflumethiazide
* Butizide
* Chlorothiazide
* Cyclopenthiazide
* Cyclothiazide
* Epitizide
* Hydrochlorothiazide#
* Hydroflumethiazide
* Mebutizide
* Methyclothiazide
* Polythiazide
* Trichlormethiazide

Thiazide-likes (primarily DCT)|

* Quinethazone
* Clopamide
* Chlortalidone
* Mefruside
* Clofenamide
* Metolazone
* Meticrane
* Xipamide
* Indapamide
* Clorexolone
* Fenquizone

Potassium-sparing (at CD)|

| ESC blockers|

* Amiloride#
* Triamterene
* Benzamil

|

Aldosterone antagonists|

* Spirolactones
* Spironolactone#
* Eplerenone
* Potassium canrenoate
* Canrenone

* Nonsteroidal
* Finerenone

Osmotic diuretics (PT, DL)|

* Mannitol#
* Glycerol
* Urea

Vasopressin receptor inhibitors
(DCT and CD)|

* Vaptans
* Conivaptan
* Mozavaptan
* Satavaptan
* Tolvaptan

* Others
* Demeclocycline
* Lithium carbonate

Other|

* Ethanol, Isopropanol, 2M2B
* mercurial diuretics (Chlormerodrin, Mersalyl, Meralluride)
* Theobromine
* Cicletanine

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Benzamil&oldid=909558"
*[CID]: Compound ID
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[VDCCs]: Voltage-dependent calcium channels
*[VGKCs]: Voltage-gated potassium channels
*[IRKs]: Inwardly rectifying potassium channel
*[KATP]: ATP-sensitive potassium channel
*[GIRK]: G protein-coupled inwardly-rectifying potassium channel
*[KCa]: Calcium-activated potassium channel
*[K2Ps]: Tandem pore domain potassium channel
*[VGSCs]: Voltage-gated sodium channels
*[ENaC]: Epithelial sodium channel
*[ASICs]: Acid-sensing ion channel
*[CaCCs]: Calcium-activated chloride channel
*[CFTR]: Cystic fibrosis transmembrane conductance regulator
*[TRPs]: Transient receptor potential channels
*[LGICs]: Ligand gated ion channels