Introduction：Basic information about BI 1744 hydrochloride CAS 869477-96-3, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
BI 1744 hydrochloride Basic information
| Product Name: | BI 1744 hydrochloride |
| Synonyms: | Olodaterol HCl;Olodaterol(BI-1744) HCl;Olodaterol(BI-1744) hydrochloride;BI 1744 hydrochloride;Olodaterol hydrochloride;BI-1744;BI 1744;BI1744;2H-1,4-Benzoxazin-3(4H)-one, 6-hydroxy-8-[(1R)-1-hydroxy-2-[[2-(4-methoxyphenyl)-1,1-dimethylethyl]amino]ethyl]-, hydrochloride (1:1);BI-1744 HCl |
| CAS: | 869477-96-3 |
| MF: | C21H27ClN2O5 |
| MW: | 422.90248 |
| EINECS: | 000-000-0 |
| Product Categories: | |
| Mol File: | 869477-96-3.mol |
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BI 1744 hydrochloride Chemical Properties
| Melting point | 153-155°C |
| storage temp. | Hygroscopic, -20°C Freezer, Under inert atmosphere |
| solubility | DMSO (Slightly), Methanol (Slightly) |
| form | Solid |
| color | Off-White to Pale Beige |
| Water Solubility | Water : 250 mg/mL (591.16 mM; Need ultrasonic) |
| Stability: | Hygroscopic |
| InChIKey | KCEHVJZZIGJAAW-QAYAHANANA-N |
| SMILES | [C@H](C1C=C(O)C=C2NC(=O)COC=12)(O)CNC(C)(C)CC1C=CC(OC)=CC=1.Cl |&1:0,r| |
Safety Information
BI 1744 hydrochloride Usage And Synthesis
| Description | Olodaterol hydrochloride was approved for long-term, oncedailymaintenance treatment of chronic obstructive pulmonarydisease (COPD) in 2013 in the following countries: Canada,Russia, United Kingdom, Denmark, and Iceland. The drughas been recommended by a federal advisory panel for approvalby the FDA. Developed and marketed by BoehringerIngelheim, olodaterol is a long-acting b2-adrenergic receptor agonistwith high selectivity over the b1- and b3-receptors (219- and1622-fold, respectively). Upon binding to and activating theb2-adrenergic receptor in the airway, olodaterol stimulates adenylcyclase to synthesize cAMP, leading to the relaxation of smoothmuscle cells in the airway. Administered by inhalation using theRespimat® Soft Mist inhaler, it delivers significant bronchodilatoreffects within five minutes of the first dose and provides sustainedimprovement in forced expiratory volume (FEV1) for over 24 h. |
| Uses | Olodaterol is a long acting β-adrenoceptor agonist used as an inhalation for treating patients with chronic obstructive pulmonary disease (COPD). |
| Definition | ChEBI: A hydrochloride obtained by combining olodaterol with one equivalent of hydrochloric acid. Used for long-term treatment of airflow obstruction in patients with chronic obstructive pulmonary disease including chronic bronchitis and/or emphysema. |
| Synthesis | Commercial 20,50-dihydroxyacetophenone (122) was treatedwith one equivalent of benzyl bromide and potassium carbonatein methylisobutylketone (MIBK) to give the 50-monobenzylatedproduct in 76% yield. Subsequent nitration occurred at the 40-positionto provide nitrophenol 123 in 87% yield. Reduction of the nitrogroup followed by subjection to chloroacetyl chloride resulted inthe construction of benzoxazine 124 in 82% yield. Next, monobrominationthrough the use of tetrabutylammonium tribromideoccurred at the acetophenone carbon to provide bromoketone125, and this was followed by asymmetric reduction of the ketoneemploying ()-DIP chloride to afford an intermediate bromohydrin,which underwent conversion to the correspondingepoxide 126 in situ upon treatment with aqueous NaOH. Thisepoxide was efficiently formed in 85% yield and 98.3% enantiomericexcess. Epoxide 126 underwent ring-opening upon subjectionto amine 127 to provide amino-alcohol 128 in in 84¨C90%yield and 89.5¨C99.5% enantiomeric purity following salt formationwith HCl. Tertiary amine 127 was itself prepared in three steps byreaction of ketone 129 with methylmagnesium chloride, Ritterreaction of the tertiary alcohol with acetonitrile, and hydrolysisof the resultant acetamide with ethanolic potassium hydroxide.Hydrogenative removal of the benzyl ether within 128 followedby recrystallization with methanolic isopropanol furnished olodaterolhydrochloride (XVI) in 63¨C70% yield. Overall, the synthesisof olodaterol hydrochloride required 10 total steps (7 linear) fromcommercially available acetophenone 122. |
| in vivo | Olodaterol (1 mg/kg; inhal.; 21 days) accelerats body weights recovery back to control levels (at day 21) and attenuats TGF-β-induced lung fibrosis[2].
Olodaterol (0.1~3 μg/kg; inhal.; 5 hours) induces a dose-dependent bronchoprotection[3].
Olodaterol (0.3 and 0.6 μg/kg; inhal.; 24 hours) induces a maximal bronchoprotection of approximately 60 % after 0.5 hours[3]. | Animal Model: | Lung fibrosis C57BL/6 mice | | Dosage: | 1 mg/mL | | Administration: | Inhal.; 21 days | | Result: | Accelerated body weight recovery back to control levels (at day 21) and attenuated TGF-β-induced lung fibrosis.| Animal Model: | Guinea Pigs | | Dosage: | 0.1~3 μg/kg | | Administration: | Inhal.; 5 hours | | Result: | Induced a dose-dependent bronchoprotection.| Animal Model: | Dogs | | Dosage: | 0.3 and 0.6 μg/kg | | Administration: | Inhal.; 24 hours | | Result: | Olodaterol (0.6 μg/kg) induced a maximal bronchoprotection of approximately 60 % after 0.5 h. |
| | IC 50 | β2 adrenoceptor: .1 nM (EC50) |
BI 1744 hydrochloride Preparation Products And Raw materials |
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