Abbott-195773

Base Information

• Chemical Name: Abbott-195773
• CAS No.: 205110-48-1
• Molecular Formula: C42H59N3O10
• Molecular Weight: 765.945
• DSSTox Substance ID: DTXSID00870225
• Wikipedia: Cethromycin
• NCI Thesaurus Code: C83613
• Metabolomics Workbench ID: 149770
• ChEMBL ID: CHEMBL3989904
• Mol file: 205110-48-1.mol

Synonyms:A 195,773;A 195773;A-195,773;A-195773;ABT 773;ABT-773;cethromycin

Chemical Property of Abbott-195773

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 211-213°
• Boiling Point: 927.1°Cat760mmHg
• PKA: 10.84±0.70(Predicted)
• Flash Point: 514.5°C
• PSA: 162.82000
• Density: 1.22g/cm³
• LogP: 5.43850
• XLogP3: 5.4
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 8
• Exact Mass: 765.42004509
• Heavy Atom Count: 55
• Complexity: 1410

Purity/Quality:

95-99% ^*data from raw suppliers

CETHROMYCIN 95.00% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1C2(C(C(C(=O)C(CC(C(C(C(=O)C(C(=O)O1)C)C)OC3C(C(CC(O3)C)N(C)C)O)(C)OCC=CC4=CC5=CC=CC=C5N=C4)C)C)NC(=O)O2)C
• Isomeric SMILES: CC[C@@H]1[C@@]2([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H](C(=O)[C@H](C(=O)O1)C)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OCC=CC4=CC5=CC=CC=C5N=C4)C)C)NC(=O)O2)C
• Recent ClinicalTrials: Study Comparing the Safety and Efficacy of Cethromycin to Clarithromycin for the Treatment of Community-Acquired Pneumonia (CAP)
• Recent EU Clinical Trials: A Double-Blinded, Randomized, Parallel group, Multi-Centre, Multi-National Comparative Study of the Safety and Efficacy of Cethromycin 300mg QD to Clarithromycin (KLACID?) 250mg BID for the treatment of Community-Acquired Pneumonia (CAP) in Adults
• Description: Cethromycin (formerly ABT-773) is a ketolide antibiotic originally developed by Abbott in the late 1990s, but abandoned in 2002. Since 2004, Advanced Life Sciences has promoted current development of cethromycin. The ketolides are structurally derived from erythromycin A and are designed to overcome resistance to macrolides. One of the main features is the lack of the neutral sugar L-cladinose at position 3 of the erythonolide ring, which is replaced by a keto group (thus giving rise to the class name). Lack of the L-cladinose moiety results in better drug absorption and less gastric irritation through improved acid stability.
• Physical properties: Cethromycin is a 6-O-ketolide, meaning that, compared with 11-Nketolides such as telithromycin, linkage with the macrolactone ring is in the 6-O-position, with an O-propylallyl linkage replacing the aminopropyl linkage of telithromycin. Cethromycin presents as a white crystalline powder. As yet, cethromycin has been used only in clinical trials and is not available for clinical use. Development is primarily directed at upper and lower respiratory tract infections.
• Uses: Antibacterial.
• Drug interactions: Ketolides and macrolides are substrates and inhibitors of the cytochrome P450 (CYP450) 3A4 system. So far, data available specifically for cethromycin are very limited and mainly exist in abstract form. It is expected that interactions are similar to other drugs that are involved in this pathway. This is exemplified by ketoconazole, a potent CYP3A4 inhibitor that caused a 5-fold increase in cethromycin AUC and a 2.5-fold increase in drug Cmax, although cethromycin’s main metabolite showed a decreased Cmax but no effect on its AUC. Similarly, rifampicin (600 mg) significantly affected the pharmacokinetics of cethromycin (300 mg), with a 95% reduction in the ketolide’s AUC and its metabolite N-desmethyl cethromycin.

Technology Process of Abbott-195773

There total 10 articles about Abbott-195773 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:

C44H61N3O11 → 10-(4-dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-4-ethyl-3a,7,9,11,13,15-hexamethyl-11-(3-quinolin-3-yl-allyloxy)-octahydro-3,5-dioxa-1-aza-cyclopentacyclotetradecene-2,6,8,14-tetraone (205110-48-1)

Guidance literature:

With methanol; Reflux;

Reference yield:

C40H72N2O13 → 10-(4-dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-4-ethyl-3a,7,9,11,13,15-hexamethyl-11-(3-quinolin-3-yl-allyloxy)-octahydro-3,5-dioxa-1-aza-cyclopentacyclotetradecene-2,6,8,14-tetraone (205110-48-1)

Guidance literature:

Multi-step reaction with 8 steps

1.1: sodium hydrogensulfite; formic acid / water; ethanol / 2.5 h / 86 °C

2.1: dmap / dichloromethane / 3 h / 20 °C

3.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -40 °C / Inert atmosphere

3.2: 28 h / -40 - 20 °C / Inert atmosphere

4.1: ammonium hydroxide / tetrahydrofuran; acetonitrile / 192 h / 20 °C / Inert atmosphere

5.1: hydrogenchloride / water; ethanol / 22 h

6.1: N-chloro-succinimide; dimethylsulfide / dichloromethane / 0.5 h / -10 - -5 °C / Inert atmosphere

6.2: 1 h / 10 °C / Inert atmosphere

7.1: triethylamine; palladium diacetate; tris-(o-tolyl)phosphine / acetonitrile / 97 h / 50 - 90 °C / Inert atmosphere

8.1: methanol / Reflux

With hydrogenchloride; methanol; dmap; ammonium hydroxide; N-chloro-succinimide; formic acid; dimethylsulfide; palladium diacetate; sodium hexamethyldisilazane; sodium hydrogensulfite; triethylamine; tris-(o-tolyl)phosphine; In tetrahydrofuran; ethanol; dichloromethane; water; acetonitrile;

Reference yield:

acetic acid 2-[4-(5-acetoxy-4-methoxy-4,6-dimethyl-tetrahydro-pyran-2-yloxy)-7-allyloxy-14-ethyl-12,13-dihydroxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yloxy]-4-dimethylamino-6-methyl-tetrahydro-pyran-3-yl ester (198557-85-6) → 10-(4-dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-4-ethyl-3a,7,9,11,13,15-hexamethyl-11-(3-quinolin-3-yl-allyloxy)-octahydro-3,5-dioxa-1-aza-cyclopentacyclotetradecene-2,6,8,14-tetraone (205110-48-1)

Guidance literature:

Multi-step reaction with 6 steps

1.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -40 °C / Inert atmosphere

1.2: 28 h / -40 - 20 °C / Inert atmosphere

2.1: ammonium hydroxide / tetrahydrofuran; acetonitrile / 192 h / 20 °C / Inert atmosphere

3.1: hydrogenchloride / water; ethanol / 22 h

4.1: N-chloro-succinimide; dimethylsulfide / dichloromethane / 0.5 h / -10 - -5 °C / Inert atmosphere

4.2: 1 h / 10 °C / Inert atmosphere

5.1: triethylamine; palladium diacetate; tris-(o-tolyl)phosphine / acetonitrile / 97 h / 50 - 90 °C / Inert atmosphere

6.1: methanol / Reflux

With hydrogenchloride; methanol; ammonium hydroxide; N-chloro-succinimide; dimethylsulfide; palladium diacetate; sodium hexamethyldisilazane; triethylamine; tris-(o-tolyl)phosphine; In tetrahydrofuran; ethanol; dichloromethane; water; acetonitrile;

upstream raw materials:

acetic acid 2-[4-(5-acetoxy-4-methoxy-4,6-dimethyl-tetrahydro-pyran-2-yloxy)-7-allyloxy-14-ethyl-12,13-dihydroxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yloxy]-4-dimethylamino-6-methyl-tetrahydro-pyran-3-yl ester

2',4-O-diacetyl-6-O-allyl-11,12-cyclocarbamate erythromycin A

acetic acid 2-(11-allyloxy-4-ethyl-8-hydroxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxo-tetradecahydro-3,5-dioxa-1-aza-cyclopentacyclotetradecen-10-yloxy)-4-dimethylamino-6-methyl-tetrahydro-pyran-3-yl ester

acetic acid 2-(11-allyloxy-4-ethyl-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxo-tetradecahydro-3,5-dioxa-1-aza-cyclopentacyclotetradecen-10-yloxy)-4-dimethylamino-6-methyl-tetrahydro-pyran-3-yl ester

Refernces