Synonym
Doripenem Free Base; S4661; S-4661; S 4661
IUPAC/Chemical Name
1-Azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid, 3-(((3S,5S)-5-(((aminosulfonyl)amino)methyl)-3-pyrrolidinyl)thio)-6-((1R)-1-hydroxyethyl)-4-methyl-7-oxo-, (4R,5S,6S)-
InChi Key
AVAACINZEOAHHE-VFZPANTDSA-N
InChi Code
InChI=1S/C15H24N4O6S2/c1-6-11-10(7(2)20)14(21)19(11)12(15(22)23)13(6)26-9-3-8(17-5-9)4-18-27(16,24)25/h6-11,17-18,20H,3-5H2,1-2H3,(H,22,23)(H2,16,24,25)/t6-,7-,8+,9+,10-,11-/m1/s1
SMILES Code
O=C(C(N12)=C(S[C@@H]3CN[C@H](CNS(=O)(N)=O)C3)[C@H](C)[C@]2([H])[C@@H]([C@H](O)C)C1=O)O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Doripenem is a new parenteral carbapenem antibiotic with broad-spectrum activity against gram-negative and gram-positive pathogens.
In vitro activity:
Doripenem, a new 1-beta-methyl carbapenem, was challenged with a worldwide collection of 394 drug-refractory isolates. For endemic extended-spectrum beta-lactamase- and stably derepressed AmpC-producing enteric bacilli, the doripenem MICs at which 90% of the isolates were inhibited (MIC90s) were 0.03 to 0.5 microg/ml, generally lower than those of comparator carbapenems. A greater proportion of strains among carbapenem-resistant nonfermentative gram-negative bacilli were inhibited by doripenem at < or =4 microg/ml, and doripenem was the most active carbapenem (MIC90, 1 to 4 microg/ml) against penicillin-resistant streptococci.
Reference: Antimicrob Agents Chemother. 2004 Aug;48(8):3136-40. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/15273134/
In vivo activity:
The bacterial counts in lung and liver tissues for all groups are shown in Table 1 and Figure 1. The lung and liver bacterial counts were statistically different between the control and treatment groups for all time points (P<0.05). At 24 h, combination therapies were more effective than doripenem monotherapy. While there were no significant differences between doripenem+sulbactam and oripenem+colistin efficacies, doripenem+amikacin showed better bactericidal activity than these treatments but the tigecycline combination did not. There were no statistical differences in the bacterial loads of lung and liver among combination therapies (P>0.05). However, all combination groups showed a better efficacy than the monotherapy group at 48 h. At 72 h, monotherapy and combination therapies showed the same results on the bacterial counts of lung and liver. Doripenem combinations with tigecycline and with amikacin showed faster bactericidal activity than with colistin and with sulbactam. The doripenem+tigecycline combination was the most effective therapy decreasing bacterial counts in all groups.
Reference: New Microbiol. 2015 Jan;38(1):67-73. http://www.newmicrobiologica.org/PUB/allegati_pdf/2015/1/67.pdf
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
60.0 |
142.68 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
420.49
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Jones RN, Huynh HK, Biedenbach DJ. Activities of doripenem (S-4661) against drug-resistant clinical pathogens. Antimicrob Agents Chemother. 2004 Aug;48(8):3136-40. doi: 10.1128/AAC.48.8.3136-3140.2004. PMID: 15273134; PMCID: PMC478547. 2. Jones RN, Huynh HK, Biedenbach DJ, Fritsche TR, Sader HS. Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations. J Antimicrob Chemother. 2004 Jul;54(1):144-54. doi: 10.1093/jac/dkh298. Epub 2004 Jun 9. PMID: 15190031.
3. Dinc G, Demiraslan H, Elmali F, Ahmed SS, Alp E, Doganay M. Antimicrobial efficacy of doripenem and its combinations with sulbactam, amikacin, colistin, tigecycline in experimental sepsis of carbapenem-resistant Acinetobacter baumannii. New Microbiol. 2015 Jan;38(1):67-73. Epub 2015 Jan 1. PMID: 25742149.
In vitro protocol:
1. Jones RN, Huynh HK, Biedenbach DJ. Activities of doripenem (S-4661) against drug-resistant clinical pathogens. Antimicrob Agents Chemother. 2004 Aug;48(8):3136-40. doi: 10.1128/AAC.48.8.3136-3140.2004. PMID: 15273134; PMCID: PMC478547. 2. Jones RN, Huynh HK, Biedenbach DJ, Fritsche TR, Sader HS. Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations. J Antimicrob Chemother. 2004 Jul;54(1):144-54. doi: 10.1093/jac/dkh298. Epub 2004 Jun 9. PMID: 15190031.
In vivo protocol:
1. Dinc G, Demiraslan H, Elmali F, Ahmed SS, Alp E, Doganay M. Antimicrobial efficacy of doripenem and its combinations with sulbactam, amikacin, colistin, tigecycline in experimental sepsis of carbapenem-resistant Acinetobacter baumannii. New Microbiol. 2015 Jan;38(1):67-73. Epub 2015 Jan 1. PMID: 25742149.
1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Doripenem. 2017 Jan 17. PMID: 31643441.
2: Paterson DL, Depestel DD. Doripenem. Clin Infect Dis. 2009 Jul 15;49(2):291-8. doi: 10.1086/600036. PMID: 19527173.
3: Anderson DL. Doripenem. Drugs Today (Barc). 2006 Jun;42(6):399-404. doi: 10.1358/dot.2006.42.6.985634. PMID: 16845443.
4: Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, Yates K, Gasink LB. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016 Sep 15;63(6):754-762. doi: 10.1093/cid/ciw378. Epub 2016 Jun 16. PMID: 27313268; PMCID: PMC4996135.
5: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006–. Doripenem. 2018 Dec 3. PMID: 29999668.
6: Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA. Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. doi: 10.2165/00003495-200767070-00006. PMID: 17488146.
7: Doripenem: S 4661. Drugs R D. 2003;4(6):363-5. doi: 10.2165/00126839-200304060-00006. PMID: 14584966.
8: Lai CC, Cheng IL, Chen YH, Tang HJ. The Efficacy and Safety of Doripenem in the Treatment of Acute Bacterial Infections-A Systemic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2019 Jul 2;8(7):958. doi: 10.3390/jcm8070958. PMID: 31269697; PMCID: PMC6679183.
9: Liu WD, Shih MC, Chuang YC, Wang JT, Sheng WH. Comparative efficacy of doripenem versus meropenem for hospital-acquired and ventilator-associated pneumonia. J Microbiol Immunol Infect. 2019 Oct;52(5):788-795. doi: 10.1016/j.jmii.2019.04.008. Epub 2019 May 14. PMID: 31155463.
10: Chahine EB, Ferrill MJ, Poulakos MN. Doripenem: a new carbapenem antibiotic. Am J Health Syst Pharm. 2010 Dec 1;67(23):2015-24. doi: 10.2146/ajhp090672. PMID: 21098373.
