138890-62-7 Usage
Description
Brinzolamide is a small molecular weight compound that has an ability to bind melanin. It is a sulfonamide and a thienothiazine, with a molecular weight of 383.5 and a melting point of about 131°C. It is a white powder or crystalline solid, which is insoluble in water, very soluble in methanol, and soluble in ethanol. Brinzolamide is a carbonic anhydrase inhibitor developed by Alcon (now Novartis) as a treatment for primary and open-angle glaucoma and ocular hypertension. It was first approved in the United States in 1998 under the trade name Azopt and is commercially formulated as a 1% ophthalmic suspension to reduce intraocular pressure (IOP).
Uses
Used in Ophthalmology:
Brinzolamide is used as an antiglaucoma drug for the treatment of increased pressure in the eye caused by open-angle glaucoma. It acts as a carbonic anhydrase inhibitor with specific affinity for carbonic anhydrase II, which is responsible for the movement of sodium and fluid transport in the eye. By inhibiting this enzyme, brinzolamide leads to a decrease in aqueous humor secretion, likely by slowing the formation of bicarbonate ions, and results in a reduction in intraocular pressure.
Used in Ocular Therapy:
Brinzolamide is used as a carbonic anhydrase inhibitor (CAI) in ocular therapy. It has been shown to produce significant reductions in IOP and demonstrated less ocular discomfort than other CAIs, such as dorzolamide.
Used in Melanin Binding Assays:
Brinzolamide has been used as a melanin binding compound or drug in melanin binding assays, which are used to study the interaction between melanin and various compounds.
Originator
Alcon (US)
Preparation
Brinzolamide synthesis method: using thiophene as raw material, 3-acetyl-2,5-dichlorothiophene (4) is obtained by chlorination and acetylation, and 4 is reacted with sodium benzyl sulfide to obtain 6,6, which is chlorinated and ammoniated. Chemical and oxidation reactions "one-pot" synthesis of 7, Carbon-based α-hydrobromination of 7 with Pyridinium tribromide gives 9,9 is asymmetrically reduced under the action of (+)-Ipc2BCl to obtain 11, which is then subjected to N-alkylation and sulfonamidation to generate (S)-3,4-dihydro-4-hydroxy-2-(3-methoxyl propyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide, the sulfonamide group was protected with trimethyl orthoacetate to give 15 , first introduce p-toluenesulfonyl group and then replace it with ethylamino group, and remove the sulfonamide group protecting group to obtain brinzolamide. The synthesis of intermediate 4 in this route is convenient, and each step of the reaction does not require column chromatography, and the total yield is 13.4%.Graphical Synthetic Routes of Olanzapine
Indications
Brinzolamide, a heterocyclic sulfonamide, is a topical CAI suspension that has a high affinity for the carbonic anhydrase II isoenzyme.Because the ocular hypotensive effect of the drug is equivalent whether dosed twice or three times daily, brinzolamide 1% may be administered twice daily.
Therapeutic Function
Antiglaucoma
Biochem/physiol Actions
Brinzolamide is a carbonic anhydrase II inhibitor used to lower intraocular pressure.
Clinical Use
Brinzolamide is indicated for the treatment of elevated IOP in patients with ocular hypertension or open-angle glaucoma.The drug is commercially available as a sterile 1.0% aqueous suspension with a pH of approximately 7.5. BAC 0.01% is added as a preservative.
The efficacy and safety of brinzolamide 1%, either two or three times daily, were evaluated in 572 patients with open-angle glaucoma or ocular hypertension against timolol 0.5% twice daily and dorzolamide 2.0% three times daily. Mean IOP changes were -3.8 to -5.7 mm Hg, -4.2 to -5.6 mm Hg, and-4.3 to-5.9 mm Hg for two- and three-times-daily brinzolamide and dorzolamide dosing, respectively. The mean IOP changes for timolol 0.5% ranged from -5.6 to -6.3 mm Hg (Figure 10-15). Brinzolamide was well tolerated, with 1.8% (twice daily) and 3% (three times daily) of patients reporting ocular discomfort versus 16.4% with dorzolamide. Complaints of blurred vision were higher with brinzolamide (5–6%) than dorzolamide (1%) or timolol (0%).
A meta-analysis of randomized clinical trials reported peak ocular hypotensive effect on IOP of 17% (19% to 15%) and trough effect of 17% (19% to 15%).
Side effects
Both brinzolamide and dorzolamide exhibit similar taste abnormalities. A single case report of the development of metabolic acidosis from topical brinzolamide has been described after twice-daily dosing. Other adverse events are negligible for brinzolamide except for some blurring of vision, attributable to its suspension vehicle.
Veterinary Drugs and Treatments
Brinzolamide is chemically similar to dorzolamide and reduces
aqueous humor production by altering H+/Na+ active transport
mechanisms associated with aqueous humor production in the ciliary
epithelial cells. It can be used as a substitute for dorzolamide
and some patients that exhibit excessive topical irritation following
application of dorzolamide drops, tolerate brinzolamide better or
vice versa. Cats seem to be particularly sensitive to irritation from
topical dorzolamide and often brinzolamide can be used in these
patients. Comparative data is available suggesting that brinzolamide
and dorzolamide are equally effective in animal patients.
Precautions
Brinzolamide has the same contraindications and precautions as dorzolamide.
references
[1] desantis l. preclinical overview of brinzolamide. surv ophthalmol. 2000 jan;44 suppl 2:s119-29.
Check Digit Verification of cas no
The CAS Registry Mumber 138890-62-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,8,8,9 and 0 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 138890-62:
(8*1)+(7*3)+(6*8)+(5*8)+(4*9)+(3*0)+(2*6)+(1*2)=167
167 % 10 = 7
So 138890-62-7 is a valid CAS Registry Number.
InChI:InChI=1/C12H21N3O5S3/c1-3-14-10-8-15(5-4-6-20-2)23(18,19)12-9(10)7-11(21-12)22(13,16)17/h7,10,14H,3-6,8H2,1-2H3,(H2,13,16,17)/t10-/m0/s1
138890-62-7Relevant articles and documents
Preparation methods of brinzolamide and an intermediate thereof
-
Paragraph 0111-0139; 0140-0167; 0168-0192, (2018/03/24)
The invention discloses preparation methods of brinzolamide and an intermediate thereof. The preparation method of the brinzolamide intermediate represented by a compound C comprises: carrying out a condensation reaction on a compound B and an orthoester-based compound at a temperature of 70-80 DEG C in an organic solvent in the presence of tertiary amine under an anhydrous condition, wherein theorthoester-based compound is one or a plurality of materials selected from trimethyl orthoacetate, triethyl orthoacetate and trimethyl orthobenzoate. According to the present invention, the condensation reaction is performed by using the tertiary amine as the catalyst, such that the reaction time for the amino protection is substantially shortened, the consumption of the protection reagent is reduced, the reaction temperature is reduced, the yield and the purity of the product are improved, the acid consumption and the alkali consumption during the post-treatment are reduced, the residue on ignition of the product is reduced, the operation is simplified, and the method is suitable for industrial production. The formulas B and C are defined in the specification.
Enantiomeric separation and simulation studies of pheniramine, oxybutynin, cetirizine, and brinzolamide chiral drugs on amylose-based columns
Ali, Imran,Al-Othman, Zeid A.,Al-Warthan, Abdulrahman,Alam, Syed Dilshad,Farooqi, Javed A.
, p. 136 - 143 (2014/03/21)
Solid phase extraction (SPE)-chiral separation of the important drugs pheniramine, oxybutynin, cetirizine, and brinzolamide was achieved on the C 18 cartridge and AmyCoat (150 x 46 mm) and Chiralpak AD (25 cm x 0.46 cm id) chiral columns in hum
Process for the preparation of brinzolamide and intermediates thereof
-
, (2011/08/07)
Preparation process of brinzolamide comprising the reaction of an halosubstituted precursor, wherein the ethylamine group is optionally protected, first with an halogen-metal exchange reaction, then with sulfur dioxide to form a sulfinate salt, and then reacting the sulfinate salt with an ammonia source. The process allows obtaining brinzolamide at an industrial scale with a high yield and high purity at reduced costs. Some new intermediates are used in this process.