(2-diethylamino-ethylsulfanyl)-acetic acid (2R,3S,4S,6R,7R,8R,14S)-3-hydroxy-2,4,7,14-tetramethyl-9-oxo-4-vinyl-tricyclo[5.4.3.1,8]tetradec-6-yl ester

ID: ALA1234521

Chembl Id: CHEMBL1234521

Cas Number: 55297-95-5

PubChem CID: 656958

Product Number: T114325M

Max Phase: Phase

Molecular Formula: C28H47NO4S

Molecular Weight: 493.75

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: SO 14055 | SQ 14055 | SQ-14055 | Tiamulin|55297-95-5|Denagard|Thiamutilin|Tiamulina|Tiamuline|Tiamulinum|Tiavet P|SQ 14055|CHEBI:44137|Tiamulin pamoate|UNII-E38WZ4U54R|Denagard (TN)|E38WZ4U54R|DTXSID2046701|SQ-14055|HSDB 7026|Tiamuline [INN-French]|Tiamulinum [INN-Latin]|EINECS 259-580-0|Tiamulina [INN-Spanish]|BRN 2229396|DTXCID00819917|Tiamulin [USAN:USP:INN:BAN]|14-Deoxy-14-((2-diethylaminoethyl-thio)-acetoxy)mutiline|SO 14055|Tiamuline (INN-French)|Tiamulinum (INN-Latin)|Tiamulina (INN-SpaniShow More

Synonyms from Alternative Forms(4): Tiamulin fumarate | Tiamulin hydrogen fumarate | SQ 22947 | SQ-22947

Canonical SMILES:  C=C[C@]1(C)C[C@@H](OC(=O)CSCCN(CC)CC)[C@]2(C)[C@H](C)CC[C@]3(CCC(=O)[C@H]32)[C@@H](C)[C@@H]1O

Standard InChI:  InChI=1S/C28H47NO4S/c1-8-26(6)17-22(33-23(31)18-34-16-15-29(9-2)10-3)27(7)19(4)11-13-28(20(5)25(26)32)14-12-21(30)24(27)28/h8,19-20,22,24-25,32H,1,9-18H2,2-7H3/t19-,20+,22-,24+,25+,26-,27+,28+/m1/s1

Standard InChI Key:  UURAUHCOJAIIRQ-QGLSALSOSA-N

Alternative Forms

  1. Parent:

    ALA1234521

    TIAMULIN
  2. Alternative Forms:

Associated Targets(Human)

ABCB1 Tchem P-glycoprotein 1 (14716 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HepG2 (196354 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
U-87 MG (3946 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HGC-27 (1452 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HT-29 (80576 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MCF7 (126967 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Staphylococcus aureus (210822 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Escherichia coli (133304 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Staphylococcus epidermidis (22802 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Abcb1a P-glycoprotein 3 (492 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mdr1a Multidrug resistance protein 1a (106 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Listeria innocua (140 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Bacillus subtilis (32866 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Enterococcus faecalis (29875 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Enterococcus faecium (13803 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
P388 (20296 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Wolbachia (153 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Streptococcus dysgalactiae (89 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Streptococcus agalactiae (1777 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Pasteurella multocida (1166 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
rpsB Bacterial 70S ribosome (328 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: YesOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: YesAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 493.75Molecular Weight (Monoisotopic): 493.3226AlogP: 4.97#Rotatable Bonds: 9
Polar Surface Area: 66.84Molecular Species: BASEHBA: 6HBD: 1
#RO5 Violations: HBA (Lipinski): 5HBD (Lipinski): 1#RO5 Violations (Lipinski):
CX Acidic pKa: CX Basic pKa: 9.51CX LogP: 4.50CX LogD: 2.41
Aromatic Rings: Heavy Atoms: 34QED Weighted: 0.28Np Likeness Score: 1.32

References

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2. Lolk L, Pøhlsgaard J, Jepsen AS, Hansen LH, Nielsen H, Steffansen SI, Sparving L, Nielsen AB, Vester B, Nielsen P..  (2008)  A click chemistry approach to pleuromutilin conjugates with nucleosides or acyclic nucleoside derivatives and their binding to the bacterial ribosome.,  51  (16): [PMID:18680270] [10.1021/jm800261u]
3. Kadlec K, Schwarz S..  (2010)  Identification of a plasmid-borne resistance gene cluster comprising the resistance genes erm(T), dfrK, and tet(L) in a porcine methicillin-resistant Staphylococcus aureus ST398 strain.,  54  (2): [PMID:20008780] [10.1128/aac.01091-09]
4. Miller K, Dunsmore CJ, Fishwick CW, Chopra I..  (2008)  Linezolid and tiamulin cross-resistance in Staphylococcus aureus mediated by point mutations in the peptidyl transferase center.,  52  (5): [PMID:18180348] [10.1128/aac.01015-07]
5. Smith LK, Mankin AS..  (2008)  Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors.,  52  (5): [PMID:18299405] [10.1128/aac.01583-07]
6. Gentry DR, McCloskey L, Gwynn MN, Rittenhouse SF, Scangarella N, Shawar R, Holmes DJ..  (2008)  Genetic characterization of Vga ABC proteins conferring reduced susceptibility to pleuromutilins in Staphylococcus aureus.,  52  (12): [PMID:18838584] [10.1128/aac.00915-08]
7. Kehrenberg C, Cuny C, Strommenger B, Schwarz S, Witte W..  (2009)  Methicillin-resistant and -susceptible Staphylococcus aureus strains of clonal lineages ST398 and ST9 from swine carry the multidrug resistance gene cfr.,  53  (2): [PMID:19047652] [10.1128/aac.01376-08]
8. Locke JB, Hilgers M, Shaw KJ..  (2009)  Mutations in ribosomal protein L3 are associated with oxazolidinone resistance in staphylococci of clinical origin.,  53  (12): [PMID:19805557] [10.1128/aac.01032-09]
9. Dai L, Wu CM, Wang MG, Wang Y, Wang Y, Huang SY, Xia LN, Li BB, Shen JZ..  (2010)  First report of the multidrug resistance gene cfr and the phenicol resistance gene fexA in a Bacillus strain from swine feces.,  54  (9): [PMID:20585133] [10.1128/aac.00169-10]
10. Kadlec K, Schwarz S..  (2009)  Novel ABC transporter gene, vga(C), located on a multiresistance plasmid from a porcine methicillin-resistant Staphylococcus aureus ST398 strain.,  53  (8): [PMID:19470508] [10.1128/aac.00570-09]
11. Locke JB, Morales G, Hilgers M, G C K, Rahawi S, José Picazo J, Shaw KJ, Stein JL..  (2010)  Elevated linezolid resistance in clinical cfr-positive Staphylococcus aureus isolates is associated with co-occurring mutations in ribosomal protein L3.,  54  (12): [PMID:20837755] [10.1128/aac.00714-10]
12. Shore AC, Brennan OM, Ehricht R, Monecke S, Schwarz S, Slickers P, Coleman DC..  (2010)  Identification and characterization of the multidrug resistance gene cfr in a Panton-Valentine leukocidin-positive sequence type 8 methicillin-resistant Staphylococcus aureus IVa (USA300) isolate.,  54  (12): [PMID:20921317] [10.1128/aac.01113-10]
13. Baggetto LG, Dong M, Bernaud J, Espinosa L, Rigal D, Bonvallet R, Marthinet E..  (1998)  In vitro and in vivo reversal of cancer cell multidrug resistance by the semi-synthetic antibiotic tiamulin.,  56  (1): [PMID:9802334] [10.1016/s0006-2952(98)00229-9]
14. Dreier I, Kumar S, Søndergaard H, Rasmussen ML, Hansen LH, List NH, Kongsted J, Vester B, Nielsen P..  (2012)  A click chemistry approach to pleuromutilin derivatives, part 2: conjugates with acyclic nucleosides and their ribosomal binding and antibacterial activity.,  55  (5): [PMID:22280300] [10.1021/jm201266b]
15. Wang X, Ling Y, Wang H, Yu J, Tang J, Zheng H, Zhao X, Wang D, Chen G, Qiu W, Tao J..  (2012)  Novel pleuromutilin derivatives as antibacterial agents: synthesis, biological evaluation and molecular docking studies.,  22  (19): [PMID:22932314] [10.1016/j.bmcl.2012.08.021]
16. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 
17. Gao ML, Zeng J, Fang X, Luo J, Jin Z, Liu YH, Tang YZ..  (2017)  Design, synthesis and antibacterial evaluation of novel pleuromutilin derivatives possessing piperazine linker.,  127  [PMID:28068600] [10.1016/j.ejmech.2017.01.004]
18. Yi Y, Xu X, Liu Y, Xu S, Huang X, Liang J, Shang R..  (2017)  Synthesis and antibacterial activities of novel pleuromutilin derivatives with a substituted pyrimidine moiety.,  126  [PMID:27940400] [10.1016/j.ejmech.2016.11.054]
19. Joshi P, Vishwakarma RA, Bharate SB..  (2017)  Natural alkaloids as P-gp inhibitors for multidrug resistance reversal in cancer.,  138  [PMID:28675836] [10.1016/j.ejmech.2017.06.047]
20. Jin Z, Wang L, Gao H, Zhou YH, Liu YH, Tang YZ..  (2019)  Design, synthesis and biological evaluation of novel pleuromutilin derivatives possessing acetamine phenyl linker.,  181  [PMID:31419741] [10.1016/j.ejmech.2019.111594]
21. Jacobs RT, Lunde CS, Freund YR, Hernandez V, Li X, Xia Y, Carter DS, Berry PW, Halladay J, Rock F, Stefanakis R, Easom E, Plattner JJ, Ford L, Johnston KL, Cook DAN, Clare R, Cassidy A, Myhill L, Tyrer H, Gamble J, Guimaraes AF, Steven A, Lenz F, Ehrens A, Frohberger SJ, Koschel M, Hoerauf A, Hübner MP, McNamara CW, Bakowski MA, Turner JD, Taylor MJ, Ward SA..  (2019)  Boron-Pleuromutilins as Anti- Wolbachia Agents with Potential for Treatment of Onchocerciasis and Lymphatic Filariasis.,  62  (5): [PMID:30730745] [10.1021/acs.jmedchem.8b01854]
22. Fan Y,Liu Y,Wang H,Shi T,Cheng F,Hao B,Yi Y,Shang R.  (2020)  Novel pleuromutilin derivatives with substituted 6-methylpyrimidine: Design, synthesis and antibacterial evaluation.,  207  [PMID:32827940] [10.1016/j.ejmech.2020.112735]
23. Zhang Z,Li K,Zhang GY,Tang YZ,Jin Z.  (2020)  Design, synthesis and biological activities of novel pleuromutilin derivatives with a substituted triazole moiety as potent antibacterial agents.,  204  [PMID:32731187] [10.1016/j.ejmech.2020.112604]
24. Huang SY, Wang X, Shen DY, Chen F, Zhang GY, Zhang Z, Li K, Jin Z, Du D, Tang YZ..  (2021)  Design, synthesis and biological evaluation of novel pleuromutilin derivatives as potent anti-MRSA agents targeting the 50S ribosome.,  38  [PMID:33857737] [10.1016/j.bmc.2021.116138]
25. Li B, Zhang Z, Zhang JF, Liu J, Zuo XY, Chen F, Zhang GY, Fang HQ, Jin Z, Tang YZ..  (2021)  Design, synthesis and biological evaluation of pleuromutilin-Schiff base hybrids as potent anti-MRSA agents in vitro and in vivo.,  223  [PMID:34153574] [10.1016/j.ejmech.2021.113624]
26. Ding R, Wang X, Fu J, Chang Y, Li Y, Liu Y, Liu Y, Ma J, Hu J..  (2022)  Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with thieno[2,3-d]pyrimidine substitution.,  237  [PMID:35468515] [10.1016/j.ejmech.2022.114398]
27. Wang X, Wang R, Zhang ZS, Zhang GY, Jin Z, Shen R, Du D, Tang YZ..  (2022)  Semisynthetic pleuromutilin antimicrobials with therapeutic potential against methicillin-resistant Staphylococcus aureus by targeting 50S ribosomal subunit.,  237  [PMID:35430480] [10.1016/j.ejmech.2022.114341]
28. Wu G, Zhu Z, Li J, Luo X, Zhu W, Liao G, Xia J, Zhang W, Pan W, Li T, Wu S..  (2022)  Design, synthesis and antibacterial evaluation of pleuromutilin derivatives.,  59  [PMID:35220163] [10.1016/j.bmc.2022.116676]
29. Yong C, Yu J, Wu C, Zhang X, Li Y, Xie C, He X, Liu D, Wang Z, Lai P, Zhang Y..  (2023)  Design, Synthesis, and Biological Activity of Thioguanine-Modified Pleuromutilin Derivatives.,  14  (6): [PMID:37312858] [10.1021/acsmedchemlett.3c00004]