Solithromycin

Solithromycin

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Systematic (IUPAC) name
(3aS,4R,7S,9R,10R,11R,13R,15R,15aR)-1-[4-[4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl]butyl]-4-ethyl-7-fluorooctahydro-11-methoxy-3a,7,9,11,13,15-hexamethyl-10-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}-2H-Oxacyclotetradecino[4,3-d]oxazole-2,6,8,14(1H,7H,9H)-tetrone
Clinical data
Legal status	Phase III clinical trials, North America, South America, Europe, Asia, S. Africa
Routes of administration	oral, intravenous
Identifiers
CAS Number	760981-83-7 Y
ATC code	none
ChemSpider	25056854
UNII	9U1ETH79CK N
ChEMBL	CHEMBL1240704 N
Synonyms	CEM-101; OP-1068
Chemical data
Formula	C43H65FN6O10
Molecular mass	845.01 g/mol
SMILES CC[C@@H]1[C@@]2([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H](C(=O)[C@](C(=O)O1)(C)F)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)N(C(=O)O2)CCCCn4cc(nn4)c5cccc(c5)N)C
InChI InChI=1S/C43H65FN6O10/c1-12-32-43(8)35(50(40(55)60-43)19-14-13-18-49-23-30(46-47-49)28-16-15-17-29(45)21-28)26(4)33(51)24(2)22-41(6,56-11)37(27(5)36(53)42(7,44)39(54)58-32)59-38-34(52)31(48(9)10)20-25(3)57-38/h15-17,21,23-27,31-32,34-35,37-38,52H,12-14,18-20,22,45H2,1-11H3/t24-,25-,26+,27+,31+,32-,34-,35-,37-,38+,41-,42+,43-/m1/s1 Key:IXXFZUPTQVDPPK-ZAWHAJPISA-N
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Solithromycin (formerly known as CEM-101 and OP-1068) is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia (CAP) and other infections.

Solithromycin exhibits excellent in vitro activity against a broad spectrum of Gram-positive respiratory tract pathogens, including macrolide-resistant strains. Solithromycin has activity against most common respiratory Gram-(+) and fastidious Gram-(-) pathogens, and is being evaluated for its utility in treating gonorrhea.

• May 2011: Solithromycin is in a Phase 2 clinical trial for serious community-acquired bacterial pneumonia (CABP) and in a Phase 1 clinical trial with an intravenous formulation.
• September 2011 : Solithromycin demonstrated comparable efficacy to levofloxacin with reduced adverse events in Phase 2 trial in people with community-acquired pneumonia
• January 2015: In a Phase 3 clinical trial for community-acquired bacterial pneumonia (CABP), Solithromycin administered orally demonstrated statistical non-inferiority to the fluoroquinolone, Moxifloxacin.
• July 2015: Patient enrollment for the second Phase 3 clinical trial (Solitaire IV) for community-acquired bacterial pneumonia (CABP) was completed with results expected in Q4 2015.
• Oct 2015: IV to oral solithromycin demonstrated statistical non-inferiority to IV to oral moxifloxacin in adults with CABP.

Structure

X-ray crystallography studies have shown solithromycin, the first fluoroketolide in clinical development, has a third region of interactions with the bacterial ribosome, as compared with two binding sites for other ketolides.

The only currently marketed ketolide, telithromycin, suffers from rare, but serious side effects. Recent studies have shown this to be likely due to the presence of the pyridine-imidazole group of the telithromycin side chain acting as an antagonist towards various nicotinic acetylcholine receptors.

Further reading

• Profile of and Research on Solithromycin