Tigecycline
[CAS 220620-09-7]

Identification

• Classification: API >> Antibiotics >> Tetracycline
• Name: Tigecycline
• Synonyms: (4S,4aS,5aR,12aS)-4,7-Bis(dimethylamino)-9-[(tert-butylamino)acetamido]-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracen-2-carboxamide
• Molecular Formula: C₂₉H₃₉N₅O₈
• Molecular Weight: 585.65
• CAS Registry Number: 220620-09-7
• EC Number: 685-736-6
• SMILES: CC(C)(C)NCC(=O)NC1=CC(=C2C[C@H]3C[C@H]4[C@@H](C(=O)C(=C([C@]4(C(=O)C3=C(C2=C1O)O)O)O)C(=O)N)N(C)C)N(C)C

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Boiling point: 890.9±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 492.6±34.3 °C (Calc.)^*
• Solubility: DMSO: 100 mg/mL, Water: 100 mg/mL (Expl.)
• Index of refraction: 1.675 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08;GHS09 Danger
• Risk Statements: H317-H318-H360-H400-H411
• Safety Statements: P201-P202-P261-P272-P273-P280-P302+P352-P305+P351+P338+P310-P308+P313-P333+P313-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Repr.	1A	H360
Skin sensitization	Skin Sens.	1	H317
Serious eye damage	Eye Dam.	1	H318
Skin irritation	Skin Irrit.	2	H315
Respiratory sensitization	Resp. Sens.	1	H334
Reproductive toxicity	Repr.	1B	H360Df
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400

• Transport Information: UN 3077

chemBlink Chemical Story

Tigecycline, CAS 220620-09-7, is a glycylcycline antibacterial developed from the tetracycline scaffold. FDA records identify it as GAR-936 and describe the chemical relationship directly: tigecycline is 9-t-butylglycylamido-minocycline. This modification was designed during efforts to overcome major mechanisms that had eroded the usefulness of older tetracyclines.

Tetracyclines inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit and interfering with entry of aminoacyl-tRNA. Bacteria, however, evolved resistance through mechanisms including active efflux and ribosomal protection proteins. Medicinal chemists found that substitution of the minocycline framework at the 9-position with a bulky glycylamido side chain could restore activity against many organisms carrying these resistance determinants. Tigecycline became the leading compound of this glycylcycline strategy.

The structural change does not create an entirely new target. Instead, it improves performance at the old tetracycline target while reducing susceptibility to important resistance mechanisms. This is a valuable lesson in antibiotic design: sometimes a successful next-generation agent comes not from discovering a new biochemical pathway but from redesigning how an established scaffold reaches and occupies its target.

The FDA approved Tygacil in 2005. Its antibacterial spectrum and intravenous formulation made it useful for serious infections in defined clinical settings. As with all antibiotics, however, activity in vitro does not mean indiscriminate use is appropriate; susceptibility, infection site, safety information and antimicrobial-stewardship principles remain important.

Chemically, tigecycline retains the dense, stereochemically rich tetracycline core and adds a tert-butylglycylamido substituent. That side chain is small compared with the whole molecule, yet it substantially changes biological behavior. Tigecycline therefore illustrates how a strategically placed substituent can revive an established antibiotic family by addressing resistance at the molecular level.

References:
1. U.S. FDA GSRS, Tigecycline, UNII 70JE2N95KR, CAS 220620-09-7.
2. U.S. FDA, Tygacil NDA 21-821 Clinical Microbiology Review, 2005.
3. Petersen PJ et al. Antimicrob Agents Chemother. 1999;43:738-744.
4. Chopra I. J Antimicrob Chemother. 2001;48:497-505.

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