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26921-17-5

26921-17-5 structure
26921-17-5 structure
  • Name: (S)-timolol maleate
  • Chemical Name: (S)-timolol maleate
  • CAS Number: 26921-17-5
  • Molecular Formula: C17H28N4O7S
  • Molecular Weight: 432.492
  • Catalog: Biochemical Inhibitor Neuronal Signaling Adrenergic Receptor Antagonist
  • Create Date: 2018-04-27 08:00:00
  • Modify Date: 2024-01-02 06:18:18
  • (S)-Timolol maleate, is a potent non-selective β-adrenergic receptor antagonist (Ki values are 1.97 and 2.0 nM for β1 and β2 receptor subtypes respectively). IC50 Value: 1.97 nM(Ki for β1); 2.0 nM(Ki for β2)Target: β-adrenergic receptor(S)-Timolol, 50% bioavailability following oral administration. Does not cross the blood brain barrier. Timolol maleate does appear to have some local anesthetic properties in human cornea after chronic use by susceptible individuals.

Name (S)-timolol maleate
Synonyms (-)-1-(tert-Butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2-propanol Maleate (1:1) (Salt)
(S)-1-[(1,1-Dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-2-propanol (Z)-2-Butenedioate (1:1) (Salt)
Timolol maleate salt
Betim
acide (2Z)-but-2-ènedioïque - (2S)-1-[(1,1-diméthyléthyl)amino]-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol (1:1)
Tenopt
(2Z)-But-2-endisäure--(2S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol(1:1)
Proflax
Aquanil
(2S)-1-[(2-Methyl-2-propanyl)amino]-3-{[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy}-2-propanol (2Z)-2-butenedioate (1:1)
Timorom
(2S)-1-(tert-Butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol (2Z)-but-2-enedioate (1:1)
(S)-Timolol maleate
Rysmon TG
EINECS 248-111-5
Optimol
(-)-Timolol Maleate
Timacar
(S)-(-)-Timolol Maleate
(2S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol (2Z)-but-2-enedioate (salt)
(2S)-1-[(1,1-Dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-2-propanol (2Z)-2-Butenedioate (1:1) (Salt)
Temserin
MFCD00058356
2-Propanol, 1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-, (2S)-, (2Z)-2-butenedioate (1:1) (salt)
Timolol maleate
(S)-Timolol (Maleate)
Description (S)-Timolol maleate, is a potent non-selective β-adrenergic receptor antagonist (Ki values are 1.97 and 2.0 nM for β1 and β2 receptor subtypes respectively). IC50 Value: 1.97 nM(Ki for β1); 2.0 nM(Ki for β2)Target: β-adrenergic receptor(S)-Timolol, 50% bioavailability following oral administration. Does not cross the blood brain barrier. Timolol maleate does appear to have some local anesthetic properties in human cornea after chronic use by susceptible individuals.
Related Catalog
References

[1]. Deepika Aggarwal, Indu P. Kaur. Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system. International Journal of Pharmaceutics. 2005, 290(1-2): 155-159.

[2]. Mandagere AK, Thompson TN, Hwang KK. Graphical model for estimating oral bioavailability of drugs in humans and other species from their Caco-2 permeability and in vitro liver enzyme metabolic stability rates. J Med Chem. 2002;45(2):304-11.

[3]. A.H El-Kamel. In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. International Journal of Pharmaceutics. 2002, 241, (1) :47-55.

[4]. Konstas AG, Maltezos AC, Gandi S, et al. Comparison of 24-hour intraocular pressure reduction with two dosing regimens of latanoprost and timolol maleate in patients with primary open-angle glaucoma. American Journal of Ophthalmology .1999, 128(1):15-20.

Boiling Point 704.6ºC at 760 mmHg
Melting Point 202-203 °C(lit.)
Molecular Formula C17H28N4O7S
Molecular Weight 432.492
Flash Point 380ºC
Exact Mass 432.167877
PSA 182.58000
LogP 0.67020
Appearance powder | white to off-white
Vapour Pressure 7.7E-21mmHg at 25°C
Storage condition Store at RT
Water Solubility H2O: soluble

Section 1. Chemical Product and Company Identification
Timolol Maleate
Common Name/
Trade Name
Timolol Maleate

Section 4. First Aid Measures
Eye ContactCheck for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at
least 15 minutes. Cold water may be used. Get medical attention if irritation occurs.
Skin ContactWash with soap and water. Cover the irritated skin with an emollient. Get medical attention if irritation develops.
Cold water may be used.
Serious Skin ContactNot available.
InhalationIf inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious InhalationNot available.
IngestionDo NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an
unconscious person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight
clothing such as a collar, tie, belt or waistband.
Serious IngestionNot available.

Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Flash PointsNot available.
Flammable LimitsNot available.
These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...), sulfur oxides (SO2, SO3...).
Products of Combustion
Fire Hazards in Presence of Slightly flammable to flammable in presence of heat.
Various SubstancesNon-flammable in presence of shocks.
Explosion Hazards in Presence Slightly explosive in presence of open flames and sparks.
of Various SubstancesNon-explosive in presence of shocks.
Fire Fighting MediaSMALL FIRE: Use DRY chemical powder.
and InstructionsLARGE FIRE: Use water spray, fog or foam. Do not use water jet.
Special Remarks onAs with most organic solids, fire is possible at elevated temperatures
Fire Hazards
Special Remarks on Explosion Fine dust dispersed in air in sufficient concentrations, and in the presence of an ignition source is a potential dust
Hazardsexplosion hazard.

Section 6. Accidental Release Measures
Small SpillUse appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by
spreading water on the contaminated surface and dispose of according to local and regional authority
requirements.
Large Spill
Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water
on the contaminated surface and allow to evacuate through the sanitary system.
Timolol Maleate

Section 7. Handling and Storage
PrecautionsKeep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not
ingest. Do not breathe dust. Wear suitable protective clothing. If ingested, seek medical advice immediately and
show the container or the label.
StorageKeep container tightly closed. Keep container in a cool, well-ventilated area. Sensitive to light.

Section 8. Exposure Controls/Personal Protection
Engineering ControlsUse process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal ProtectionSafety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used
a Large Spillto avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist
BEFORE handling this product.
Exposure LimitsNot available.

Section 9. Physical and Chemical Properties
Physical state and appearance Solid. (Crystalline powder. Crystals solid.)OdorOdorless.
TasteNot available.
Molecular Weight432.49 g/mole
ColorWhite. Off-white.
pH (1% soln/water)Not available.
Not available.
Boiling Point
Melting PointDecomposition temperature: 199°C (390.2°F)
Not available.
Critical Temperature
Specific GravityNot available.
Vapor PressureNot applicable.
Vapor DensityNot available.
VolatilityNot available.
Odor ThresholdNot available.
Water/Oil Dist. Coeff.Not available.
Ionicity (in Water)Not available.
Dispersion PropertiesSee solubility in water.
SolubilitySoluble in cold water.
Insoluble in diethyl ether.
Sparingly soluble in chloroform.
Soluble in ethanol.

Section 10. Stability and Reactivity Data
StabilityThe product is stable.
Instability TemperatureNot available.
Conditions of InstabilityExcess heat, dust generation, light
Incompatibility with various Not available.
substances
Timolol Maleate
Not available.
Corrosivity
Special Remarks onSensitive to light.
Reactivity
Special Remarks onNot available.
Corrosivity
Will not occur.
Polymerization

Section 11. Toxicological Information
Routes of EntryInhalation. Ingestion.
Toxicity to AnimalsAcute oral toxicity (LD50): 1028 mg/kg [Rat].
Chronic Effects on Humans Not available.
Other Toxic Effects onSlightly hazardous in case of skin contact (irritant), of ingestion, of inhalation.
Humans
Special Remarks onNot available.
Toxicity to Animals
Special Remarks onNot available.
Chronic Effects on Humans
Special Remarks on otherAcute Potential Health Effects:
Toxic Effects on HumansSkin: May cause skin irritation.
Eyes: May cause eye irritation.
Inhalation: May cause respiratory tract and mucous membrane irritation.
Ingestion: May be harmful if swallowed. May cause nausea, vomiting, diarrhea, fatigue, bradycardia, congestive
heart failure, heart block, hypertension, cold extremities, depression, convulsions, tremor, somnolence, and
disturbances of sleep and vision. May also affect respiration (dyspnea), urinary system, liver, and spleen.

Section 12. Ecological Information
EcotoxicityNot available.
BOD5 and CODNot available.
Products of BiodegradationPossibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
Toxicity of the ProductsThe products of degradation are less toxic than the product itself.
of Biodegradation
Not available.
Special Remarks on the
Products of Biodegradation

Section 13. Disposal Considerations
Waste DisposalWaste must be disposed of in accordance with federal, state and local environmental
control regulations.
Timolol Maleate

Section 14. Transport Information
DOT ClassificationNot a DOT controlled material (United States).
IdentificationNot applicable.
Not applicable.
Special Provisions for
Transport
DOT (Pictograms)

Section 15. Other Regulatory Information and Pictograms
No products were found.
Federal and State
Regulations
CaliforniaCalifornia prop. 65: This product contains the following ingredients for which the State of California has found
to cause cancer which would require a warning under the statute: No products were found.
Proposition 65
Warnings
California prop. 65: This product contains the following ingredients for which the State of California has found
to cause birth defects which would require a warning under the statute: No products were found.
Other RegulationsEINECS: This product is on the European Inventory of Existing Commercial Chemical Substances.
Other ClassificationsWHMIS (Canada) Not controlled under WHMIS (Canada).
DSCL (EEC)R22- Harmful if swallowed.S2- Keep out of the reach of children.
S46- If swallowed, seek medical advice
immediately and show this container or label.
Health Hazard
HMIS (U.S.A.)1 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
1 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
TDG (Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Timolol Maleate
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or
equivalent.


SECTION 16 - ADDITIONAL INFORMATION
N/A

CHEMICAL IDENTIFICATION

RTECS NUMBER :
UA8475000
CAS REGISTRY NUMBER :
26921-17-5
LAST UPDATED :
199512
DATA ITEMS CITED :
11
MOLECULAR FORMULA :
C13-H24-N4-O3-S.C4-H4-O4
MOLECULAR WEIGHT :
432.55
WISWESSER LINE NOTATION :
T6N DOTJ A- DT5NSNJ EO1YQ1MX1&1&1 &QV1U1VQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Ocular
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
39 mg/kg/87W-I
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 143,1627,1983
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Ocular
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
5 ug/kg
TOXIC EFFECTS :
Cardiac - other changes Lungs, Thorax, or Respiration - structural or functional change in trachea or bronchi
REFERENCE :
JFAPDE Journal of Family Practice. (Appleton and Lange, East Norwalk, CT) V.1- 1974- Volume(issue)/page/year: 32,97,1991
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
1028 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,464,1982
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
381 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 32,1393,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
881 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,464,1982
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
1137 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 12,1204,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
300 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity) Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 32,1393,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
805 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 12,1204,1981 ** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
52500 mg/kg/25W-I
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity) Gastrointestinal - changes in structure or function of salivary glands Kidney, Ureter, Bladder - urine volume increased
REFERENCE :
YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 32,1393,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
3500 mg/kg/5W-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis Liver - changes in liver weight Blood - changes in spleen
REFERENCE :
YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 32,1393,1981 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3219 No. of Facilities: 82 (estimated) No. of Industries: 2 No. of Occupations: 11 No. of Employees: 5070 (estimated) No. of Female Employees: 2032 (estimated)
Symbol GHS07 GHS08
GHS07, GHS08
Signal Word Warning
Hazard Statements H302-H361
Precautionary Statements P280-P301 + P312 + P330
Personal Protective Equipment Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
Hazard Codes Xn,Xi
Risk Phrases R22
Safety Phrases S36
RIDADR NONH for all modes of transport
WGK Germany 3
RTECS UA8475000
HS Code 2934999090
HS Code 2934999090
Summary 2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%