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Chemistry

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Also known as: 308242-62-8, Cns 7056, Cns-7056, Ono-2745, 7v4a8u16mb, 308242-62-8 (freee base)
Molecular Formula
C21H19BrN4O2
Molecular Weight
439.3  g/mol
InChI Key
CYHWMBVXXDIZNZ-KRWDZBQOSA-N
FDA UNII
7V4A8U16MB

Remimazolam Besylate
Remimazolam is a short-acting benzodiazepine derivative that is structurally related to midazolam, with sedative-hypnotic activity. Upon administration, remimazolam targets and binds to a specific site on the gamma-aminobutyric acid (GABA)-A-chloride ionophore receptor complex located on the neuronal membrane. Binding causes an allosteric modification of the receptor thereby enhancing the affinity of GABA to the receptor leading to an increase in the frequency of chloride-channel opening events, which leads to an increase in chloride ion conductance, neuronal hyperpolarization, inhibition of the action potential, and a decrease in neuronal excitability.
1 2D Structure

Remimazolam Besylate

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
methyl 3-[(4S)-8-bromo-1-methyl-6-pyridin-2-yl-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]propanoate
2.1.2 InChI
InChI=1S/C21H19BrN4O2/c1-13-12-24-21-17(7-9-19(27)28-2)25-20(16-5-3-4-10-23-16)15-11-14(22)6-8-18(15)26(13)21/h3-6,8,10-12,17H,7,9H2,1-2H3/t17-/m0/s1
2.1.3 InChI Key
CYHWMBVXXDIZNZ-KRWDZBQOSA-N
2.1.4 Canonical SMILES
CC1=CN=C2N1C3=C(C=C(C=C3)Br)C(=NC2CCC(=O)OC)C4=CC=CC=N4
2.1.5 Isomeric SMILES
CC1=CN=C2N1C3=C(C=C(C=C3)Br)C(=N[C@H]2CCC(=O)OC)C4=CC=CC=N4
2.2 Other Identifiers
2.2.1 UNII
7V4A8U16MB
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Cns 7056

2. Methyl 3-(8-bromo-1-methyl-6-(2-pyridinyl)-4h-imidazo(1,2-a)(1,4)benzodiazepin-4-yl)propanoate

3. Ono 2745

4. Ono-2745

5. Ono2745

2.3.2 Depositor-Supplied Synonyms

1. 308242-62-8

2. Cns 7056

3. Cns-7056

4. Ono-2745

5. 7v4a8u16mb

6. 308242-62-8 (freee Base)

7. 4h-imidazo(1,2-a)(1,4)benzodiazepine-4-propanoic Acid, 8-bromo-1-methyl-6-(2-pyridinyl)-, Methyl Ester, (4s)-

8. Methyl (s)-3-(8-bromo-1-methyl-6-(pyridin-2-yl)-4h-benzo[f]imidazo[1,2-a][1,4]diazepin-4-yl)propanoate

9. Remimazolam [inn]

10. Unii-7v4a8u16mb

11. Remimazolam [mi]

12. Remimazolam (usan/inn)

13. Remimazolam [usan:inn]

14. Remimazolam [usan]

15. Remimazolam [who-dd]

16. Schembl846435

17. Chembl4297526

18. Dtxsid20953024

19. Ono2745

20. Amy15524

21. Ex-a5536

22. Ono 2745

23. Who 9232

24. Zinc3927450

25. Akos025213215

26. Db12404

27. Hy-14867

28. 4523b

29. Cs-0003605

30. D11788

31. 4h-imidazol(1,2-a)(1,4)benzodiazepine-4-propionic Acid, (s)-

32. (s)-methyl 3-(8-bromo-1-methyl-6-(pyridin-2-yl)-4h-benzo[f]imidazo[1,2-a][1,4]diazepin-4-yl)propanoate

33. Methyl 3-((4s)-8-bromo-1-methyl-6-(pyridin-2-yl)-4h-imidazo(1,2-a)(1,4)benzodiazepin-4-yl)propanoate

34. Methyl 3-[(4s)-8-bromo-1-methyl-6-(2-pyridyl)-4h-imidazo[1,2-a][1,4]benzodiazepin-4-yl]propanoate

35. Methyl 3-[(4s)-8-bromo-1-methyl-6-pyridin-2-yl-4h-imidazo[1,2-a][1,4]benzodiazepin-4-yl]propanoate

36. Methyl 3-[8-bromo-1-methyl-6-(pyridin-2-yl)-4h-imidazo[1,2-a][1,4]benzodiazepin-4-yl]propanoate

2.4 Create Date
2006-10-25
3 Chemical and Physical Properties
Molecular Weight 439.3 g/mol
Molecular Formula C21H19BrN4O2
XLogP33.4
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count5
Rotatable Bond Count5
Exact Mass438.06914 g/mol
Monoisotopic Mass438.06914 g/mol
Topological Polar Surface Area69.4 Ų
Heavy Atom Count28
Formal Charge0
Complexity601
Isotope Atom Count0
Defined Atom Stereocenter Count1
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Remimazolam is indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.


FDA Label


Remimazolam is indicated in adults for procedural sedation.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Remimazolam modulates the effects of GABA(A) receptors in order to enhance the effects of GABA. It is considered an "ultra short-acting" benzodiazepine that achieves peak sedation within 3 to 3.5 minutes following intravenous administration, a property that makes it desirable for use during short procedures. Hepatic impairment can result in elevated serum levels of remimazolam - patients with severe hepatic impairment should be carefully titrated to effect. As of its approval date, remimazolam has not received a scheduling action by the DEA under the Controlled Substances Act. As benzodiazepines as a class have been implicated in the development of drug dependence and have a known potential for abuse, remimazolam should be used with caution in patients with a history of drug dependence or abuse.


5.2 ATC Code

N05CD


N - Nervous system

N05 - Psycholeptics

N05C - Hypnotics and sedatives

N05CD - Benzodiazepine derivatives

N05CD14 - Remimazolam


5.3 Absorption, Distribution and Excretion

Absorption

The Cmax and AUC0-inf following intravenous administration of 0.01 to 0.5 mg/kg were 189 to 6,960 ng/mL and 12.1 to 452 ngh/mL, respectively, and appear to be relatively dose proportional. The Tmax of the inactive CNS7054 metabolite is approximately 20-30 minutes and its AUC0-inf ranges from 231 to 7,090 ngh/mL.


Route of Elimination

In patients undergoing colonoscopy, approximately 0.003% of the administered dose is excreted in the urine as unchanged parent drug and 50-60% is excreted in the urine as CNS7054. In healthy subjects, >80% of the administered dose is excreted in the urine as CNS7054.


Volume of Distribution

The volume of distribution is approximately 0.76 - 0.98 L/kg.


Clearance

The clearance of remimazolam is approximately 24 - 75 L/h and is independent of body weight.


5.4 Metabolism/Metabolites

Remimazolam does not appear to undergo biotransformation via hepatic cytochrome P450 enzymes, nor does it induce or inhibit these enzymes. Its primary route of metabolism is hydrolysis via hepatic carboxylesterase-1 (CES1) to yield the inactive CNS7054 metabolite, which then undergoes glucuronidation and hydroxylation prior to elimination. CNS7054 possesses a 300-fold lesser affinity for GABA(A) receptors as compared to the parent drug.


5.5 Biological Half-Life

Following intravenous administration, the distribution half-life is of remimazolam is 0.5 - 2 minutes and the terminal elimination half-life is 37 - 53 minutes. Half-life is increased in patients with hepatic impairment necessitating careful dose titration in this population. The half-life of remimazolam's major inactive metabolite, CNS7054, is 2.4 - 3.8 hours.


5.6 Mechanism of Action

Like other benzodiazepines, remimazolam exerts its therapeutic effects by potentiating the effect of gamma-aminobutyric acid (GABA) on GABA(A) receptors, the main inhibitory neurotransmitter receptors in the mammalian brain. GABA(A) receptors are a component of GABA-gated ionotropic chloride channels that produce inhibitory postsynaptic potentials - following activation by GABA, the channel undergoes a conformational change that allows the passage of chloride ions through the channel. The inhibitory potentials produced by GABA neurotransmission play an integral role in the suppression and control of epileptiform nerve firing such as that seen in epilepsy, which makes the GABA system a desirable target in the treatment of epilepsy. Benzodiazepines are positive allosteric modulators of GABA(A) function. They bind to the interface between alpha () and gamma () subunits on the receptor, commonly referred to as the benzodiazepine binding site, and modulate the receptor such that its inhibitory response to GABA binding is dramatically increased.


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19-Dec-2023
09-Sep-2024
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Remimazolam manufacturers, exporters & distributors 1

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PharmaCompass offers a list of Remimazolam API manufacturers, exporters & distributors, which can be sorted by GMP, USDMF, JDMF, KDMF, CEP (COS), WC, Price,and more, enabling you to easily find the right Remimazolam manufacturer or Remimazolam supplier for your needs.

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API | Excipient name

Remimazolam

Synonyms

308242-62-8, Cns 7056, Cns-7056, Ono-2745, 7v4a8u16mb, 308242-62-8 (freee base)

Cas Number

308242-62-8

Unique Ingredient Identifier (UNII)

7V4A8U16MB

About Remimazolam

Remimazolam is a short-acting benzodiazepine derivative that is structurally related to midazolam, with sedative-hypnotic activity. Upon administration, remimazolam targets and binds to a specific site on the gamma-aminobutyric acid (GABA)-A-chloride ionophore receptor complex located on the neuronal membrane. Binding causes an allosteric modification of the receptor thereby enhancing the affinity of GABA to the receptor leading to an increase in the frequency of chloride-channel opening events, which leads to an increase in chloride ion conductance, neuronal hyperpolarization, inhibition of the action potential, and a decrease in neuronal excitability.

Remimazolam Besylate Manufacturers

A Remimazolam Besylate manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Remimazolam Besylate, including repackagers and relabelers. The FDA regulates Remimazolam Besylate manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Remimazolam Besylate API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Remimazolam Besylate manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Remimazolam Besylate Suppliers

A Remimazolam Besylate supplier is an individual or a company that provides Remimazolam Besylate active pharmaceutical ingredient (API) or Remimazolam Besylate finished formulations upon request. The Remimazolam Besylate suppliers may include Remimazolam Besylate API manufacturers, exporters, distributors and traders.

click here to find a list of Remimazolam Besylate suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Remimazolam Besylate USDMF

A Remimazolam Besylate DMF (Drug Master File) is a document detailing the whole manufacturing process of Remimazolam Besylate active pharmaceutical ingredient (API) in detail. Different forms of Remimazolam Besylate DMFs exist exist since differing nations have different regulations, such as Remimazolam Besylate USDMF, ASMF (EDMF), JDMF, CDMF, etc.

A Remimazolam Besylate DMF submitted to regulatory agencies in the US is known as a USDMF. Remimazolam Besylate USDMF includes data on Remimazolam Besylate's chemical properties, information on the facilities and procedures used, and details about packaging and storage. The Remimazolam Besylate USDMF is kept confidential to protect the manufacturer’s intellectual property.

click here to find a list of Remimazolam Besylate suppliers with USDMF on PharmaCompass.

Remimazolam Besylate KDMF

In Korea, the Ministry of Food and Drug Safety (MFDS) is in charge of regulating pharmaceutical products and services.

Pharmaceutical companies submit a Remimazolam Besylate Drug Master File in Korea (Remimazolam Besylate KDMF) to the MFDS, which includes comprehensive information about the production, processing, facilities, materials, packaging, and testing of Remimazolam Besylate. The MFDS reviews the Remimazolam Besylate KDMF as part of the drug registration process and uses the information provided in the Remimazolam Besylate KDMF to evaluate the safety and efficacy of the drug.

After submitting a Remimazolam Besylate KDMF to the MFDS, the registered manufacturer can provide importers or distributors with the registration number without revealing confidential information to Korean business partners. Applicants seeking to register their Remimazolam Besylate API can apply through the Korea Drug Master File (KDMF).

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Remimazolam Besylate NDC

National Drug Code is a comprehensive database maintained by the FDA that contains information on all drugs marketed in the US. This directory includes information about finished drug products, unfinished drug products, and compounded drug products, including those containing Remimazolam Besylate as an active pharmaceutical ingredient (API).

Finished drug products

The FDA updates the NDC directory daily. The NDC numbers for Remimazolam Besylate API and other APIs are published in this directory by the FDA.

Unfinished drugs

The NDC unfinished drugs database includes product listing information submitted for all unfinished drugs, such as active pharmaceutical ingredients (APIs), drugs intended for further processing and bulk drug substances for compounding.

Pharmaceutical companies that manufacture Remimazolam Besylate as an active pharmaceutical ingredient (API) must furnish the FDA with an updated record of all drugs that they produce, prepare, propagate, compound, or process for commercial distribution in the US at their facilities.

Compounded drug products

The NDC directory also contains data on finished compounded human drug products that contain Remimazolam Besylate and are produced by outsourcing facilities. While these outsourcing facilities are not mandated to assign a Remimazolam Besylate NDC to their finished compounded human drug products, they may choose to do so.

click here to find a list of Remimazolam Besylate suppliers with NDC on PharmaCompass.

Remimazolam Besylate GMP

Remimazolam Besylate Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Remimazolam Besylate GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Remimazolam Besylate GMP manufacturer or Remimazolam Besylate GMP API supplier for your needs.

Remimazolam Besylate CoA

A Remimazolam Besylate CoA (Certificate of Analysis) is a formal document that attests to Remimazolam Besylate's compliance with Remimazolam Besylate specifications and serves as a tool for batch-level quality control.

Remimazolam Besylate CoA mostly includes findings from lab analyses of a specific batch. For each Remimazolam Besylate CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Remimazolam Besylate may be tested according to a variety of international standards, such as European Pharmacopoeia (Remimazolam Besylate EP), Remimazolam Besylate JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Remimazolam Besylate USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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