ID: ALA1234521

Max Phase: Phase

Molecular Formula: C28H47NO4S

Molecular Weight: 493.75

Molecule Type: Small molecule

Representations

Synonyms (3): SO 14055 | SQ 14055 | SQ-14055
Synonyms from Alternative Forms(3):

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

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 493.75

Molecular Weight (Monoisotopic): 493.3226

AlogP: 4.97

#Rotatable Bonds: 9

Polar Surface Area: 66.84

Molecular Species: BASE

HBA: 6

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 9.51

CX LogP: 4.50

CX LogD: 2.41

Aromatic Rings: 0

Heavy Atoms: 34

QED Weighted: 0.28

Np Likeness Score: 1.32

References

1. Gentry DR, Rittenhouse SF, McCloskey L, Holmes DJ..  (2007)  Stepwise exposure of Staphylococcus aureus to pleuromutilins is associated with stepwise acquisition of mutations in rplC and minimally affects susceptibility to retapamulin.,  51  (6): [PMID:17404009] [10.1128/aac.01066-06]

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]

Source

Source(3):

• Scientific Literature
• USP Dictionary of USAN and International Drug Names
• TP-search Transporter Database