(R)-(+)-Timolol Maleate

Base Information

• Chemical Name: (R)-(+)-Timolol Maleate
• CAS No.: 26921-17-5
• Molecular Formula: C13H24N4O3S^.C4H4O4
• Molecular Weight: 432.498
• Hs Code.: 29349990
• European Community (EC) Number: 256-854-1,248-034-7
• NSC Number: 757351
• UNII: 78U14B243Y
• Wikidata: Q27266692
• Mol file: 26921-17-5.mol

Synonyms:(R)-(+)-Timolol Maleate;D-Timolol maleate;26839-77-0;(+)-Timolol maleate;50929-98-1;Timolol maleate, R-enantiomer;(R)-Timolol hydrogen maleate;UNII-78U14B243Y;EINECS 248-034-7;78U14B243Y;(Z)-but-2-enedioic acid;(2R)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol;(R)-bis[3-[3-(tert-butylamino)-2-hydroxypropoxy]-4-morpholino-1,2,5-thiadiazole] maleate;(R)-Timolol maleate;(+)-3-(3-(tert-Butylamino)-2-hydroxypropoxy)-4-morpholino-1,2,5-thiadiazole maleate;(R)-Bis(3-(3-(tert-butylamino)-2-hydroxypropoxy)-4-morpholino-1,2,5-thiadiazole) maleate;Dextimolol Maleate;C13-H24-N4-O3-S.C4-H4-O4;R-enantiomertimolol maleate;SPECTRUM1500578;TIMOLOL MALEATE, (R)-;HMS500I20;TIMOLOL MALEATE, (+)-;(+)-3-[3-(tert-butylamino)-2-hydroxypropoxy]-4-morpholino-1,2,5-thiadiazole maleate;HMS1921E15;Pharmakon1600-01500578;EINECS 256-854-1;CCG-39272;NSC757351;NCGC00094794-01;NCGC00094794-02;(R)-(+)-3-Morpholino-4-(3-tert-butylamino-2-hydroxypropoxy)-1,2,5-thiadiazole Hydrogen Maleate;J369.187J;TIMOLOL MALEATE, R-ENANTIOMER [WHO-DD];J-019136;Q27266692;(+)-3-(3-tert-Butylamino-2-hydroxypropoxy)-4-morpholino-1,2,5-thiadiazole hydrogen maleate;(2R)-1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-2-PROPANOL (2Z)-2-BUTENEDIOATE SALT;(2R)-1-((2-METHYL-2-PROPANYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-2-PROPANOL (2Z)-2-BUTENEDIOATE (1:1);(Z)-BUT-2-ENEDIOIC ACID, (2R)-1-(TERT-BUTYLAMINO)-3-((4-MORPHOLIN-4-YL-1,2,5-THIADIAZOL-3-YL)OXY)PROPAN-2-OL;2-PROPANOL, 1-((1,1-DIMETHYLETHYL)AMINO)-3-((4-(4-MORPHOLINYL)-1,2,5-THIADIAZOL-3-YL)OXY)-, (2R)-, (2Z)-2-BUTENEDIOATE (1:1);2-PROPANOL, 1-(TERT-BUTYLAMINO)-3-((4-MORPHOLINO-1,2,5-THIADIAZOL-3-YL)OXY)-, (+)-, MALEATE (1:1) (SALT), (-)-;2-Propanol, 1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-, (+)-, (Z)-2-butenedioate (1:1) (salt)

Chemical Property of (R)-(+)-Timolol Maleate

Chemical Property:

• Vapor Pressure: 7.7E-21mmHg at 25°C
• Melting Point: 202-203 °C(lit.)
• Boiling Point: 487.2 °C at 760 mmHg
• Flash Point: 248.5 °C
• PSA: 182.58000
• LogP: 0.67020
• Storage Temp.: Store at RT
• Solubility.: H2O: soluble
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 9
• Exact Mass: 432.16787042
• Heavy Atom Count: 29
• Complexity: 429

Purity/Quality:

98%-102% ^*data from raw suppliers

Timolol Maleate ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi,Xn
• Hazard Codes: Xn,Xi
• Statements: 22-63-36/37/38
• Safety Statements: 36-37/39-26

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CC(C)(C)NCC(COC1=NSN=C1N2CCOCC2)O.C(=CC(=O)O)C(=O)O
• Isomeric SMILES: CC(C)(C)NC[C@H](COC1=NSN=C1N2CCOCC2)O.C(=C\C(=O)O)\C(=O)O
• Recent EU Clinical Trials: A phase IV study on the changes in ocular signs and symptoms in patients
• Description: Timolol is a non-selective β-adrenergic receptor antagonist with log Kd values of -8.27, -9.86, and -6.8 for binding to human β1-, β2-, and β3-adrenoceptors, respectively. It has been reported that only the (S) enantiomer contributes to the β-blocking effects of racemic timolol, but the weakly active (R) isomer maintains a beneficial effect on intraocular pressure without the undesirable side-effect of bronchial constriction caused by non-selective action of (S)-timolol on β1 and β2 receptors. Timolol has been use alone and in fixed combinations with either prostaglandin analogs or carbonic anhydrase inhibitors to reduce intraocular pressure in research models of ocular hypertension and glaucoma.
• Uses: betaadrenergic blocker Anti hypertensive, Anti-glaucoma
• Clinical Use: Beta-adrenoceptor blocker: Hypertension Angina Glaucoma Migraine prophylaxis
• Drug interactions: Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: NSAIDs antagonise hypotensive effect. Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide. Antidepressants: enhanced hypotensive effect with MAOIs. Antihypertensives: enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin. Antimalarials: increased risk of bradycardia with mefloquine. Antipsychotics: enhanced hypotensive effect with phenothiazines. Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil. Cytotoxics: possible increased risk of bradycardia with crizotinib. Diuretics: enhanced hypotensive effect. Fingolimod: possibly increased risk of bradycardia. Moxisylyte: possible severe postural hypotension. Sympathomimetics: severe hypertension with adrenaline and noradrenaline and possibly with dobutamine; also response to adrenaline may be reduced.

Technology Process of (R)-(+)-Timolol Maleate

There total 10 articles about (R)-(+)-Timolol Maleate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

timolol (26839-75-8,47148-57-2) + maleic acid (110-16-7,26099-09-2) → timolol maleate (26921-17-5)

Guidance literature:

In tetrahydrofuran; at 25 ℃; for 1h;

DOI:10.1016/j.tet.2007.01.057

Reference yield:

3-hydroxy-4-(N-morpholino)-1,2,5-thiadiazole (30165-97-0) → timolol maleate (26921-17-5)

Guidance literature:

Multi-step reaction with 4 steps

1: 95 percent / potassium tert-butoxide / tetrahydrofuran / 5 h / 25 °C

2: acetic acid / (S,S)-salen-cobalt(II) / tetrahydrofuran; H₂O / 8 h / 0 - 20 °C

3: 66 percent / KI / 72 h / Heating

4: tetrahydrofuran / 1 h / 25 °C

With potassium tert-butylate; acetic acid; potassium iodide; (S,S)-salen-cobalt(II); In tetrahydrofuran; water;

DOI:10.1016/j.tet.2007.01.057

Reference yield:

4-{4-[(2R/S)-oxiran-2-ylmethoxy]-1,2,5-thiadiazol-3-yl}morpholine (58827-68-2) → timolol maleate (26921-17-5)

Guidance literature:

Multi-step reaction with 3 steps

1: acetic acid / (S,S)-salen-cobalt(II) / tetrahydrofuran; H₂O / 8 h / 0 - 20 °C

2: 66 percent / KI / 72 h / Heating

3: tetrahydrofuran / 1 h / 25 °C

With acetic acid; potassium iodide; (S,S)-salen-cobalt(II); In tetrahydrofuran; water;

DOI:10.1016/j.tet.2007.01.057

upstream raw materials:

timolol

maleic acid

(S)-5-((4-morpholino-1,2,5-thiadiazol-3-yloxy)-methyl)-3-tert-butyloxazolidin-2-one

3-hydroxy-4-(N-morpholino)-1,2,5-thiadiazole

Downstream raw materials:

timolol

Refernces

• 1、 Narina, Srinivasarao V.,Sudalai, Arumugam. "Enantioselective synthesis of (S)-timolol via kinetic resolution of terminal epoxides and dihydroxylation of allylamines". . p. 3026 - 3030. Retrieved 2007/10/03.