(3R,4R,5S)-4-Acetylamino-3-(1-ethyl-propoxy)-5-guanidino-cyclohex-1-enecarboxylic acid

ID: ALA81717

Chembl Id: CHEMBL81717

PubChem CID: 490476

Max Phase: Preclinical

Molecular Formula: C15H26N4O4

Molecular Weight: 326.40

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Guanidino-Oseltamivir Carboxylicacid | CHEMBL81717|Guanidino-Oseltamivir Carboxylicacid|BDBM5013|SCHEMBL1149242|BDBM50028503|(3R,4R,5S)-4-acetamido-3-(1-ethylpropoxy)-5-guanidino-cyclohexene-1-carboxylic acid|(3r,4r,5s)-4-acetamido-5-guanidinyl-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid|(3R,4R,5S)-4-(Acetylamino)-5-{[amino(iminomethyl)]amino}-3-[(1-ethylpropyl)oxy]-1-cyclohexene-1-carboxylic acid|(3R,4R,5S)-5-carbamimidamido-4-acetamido-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylic acid

Canonical SMILES:  CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NC(=N)N)[C@H]1NC(C)=O

Standard InChI:  InChI=1S/C15H26N4O4/c1-4-10(5-2)23-12-7-9(14(21)22)6-11(19-15(16)17)13(12)18-8(3)20/h7,10-13H,4-6H2,1-3H3,(H,18,20)(H,21,22)(H4,16,17,19)/t11-,12+,13+/m0/s1

Standard InChI Key:  TXXPTEJSSVMAFL-YNEHKIRRSA-N

Alternative Forms

1. Parent:

   

   ALA81717

   Guanidino-Oseltamivir Carboxylicacid

2. Alternative Forms:

   

   ALA81717

   (3R,4R,5S)-4-acetamido-5-(diaminomethylideneamino)-3-pentan-3-yloxycyclohexene-1-carboxylic acid;2,2,2-trifluoroacetic acid

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 326.40

Molecular Weight (Monoisotopic): 326.1954

AlogP: 0.33

#Rotatable Bonds: 7

Polar Surface Area: 137.53

Molecular Species: ZWITTERION

HBA: 4

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 4.10

CX Basic pKa: 11.93

CX LogP: -1.55

CX LogD: -1.55

Aromatic Rings: ┄

Heavy Atoms: 23

QED Weighted: 0.34

Np Likeness Score: 1.07

References

1. Kim CU, Lew W, Williams MA, Wu H, Zhang L, Chen X, Escarpe PA, Mendel DB, Laver WG, Stevens RC..  (1998)  Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors.,  41  (14): [PMID:9651151] [10.1021/jm980162u]

2. Lü WJ, Chen YL, Ma WP, Zhang XY, Luan F, Liu MC, Chen XG, Hu ZD..  (2008)  QSAR study of neuraminidase inhibitors based on heuristic method and radial basis function network.,  43  (3): [PMID:18255197] [10.1016/j.ejmech.2007.04.011]

3. Liu KC, Lee PS, Wang SY, Cheng YS, Fang JM, Wong CH..  (2011)  Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir.,  19  (16): [PMID:21778065] [10.1016/j.bmc.2011.06.080]

4. Cheng TJ, Weinheimer S, Tarbet EB, Jan JT, Cheng YS, Shie JJ, Chen CL, Chen CA, Hsieh WC, Huang PW, Lin WH, Wang SY, Fang JM, Hu OY, Wong CH..  (2012)  Development of oseltamivir phosphonate congeners as anti-influenza agents.,  55  (20): [PMID:23009169] [10.1021/jm3008486]

5. Schade D, Kotthaus J, Riebling L, Kotthaus J, Müller-Fielitz H, Raasch W, Koch O, Seidel N, Schmidtke M, Clement B..  (2014)  Development of novel potent orally bioavailable oseltamivir derivatives active against resistant influenza A.,  57  (3): [PMID:24422530] [10.1021/jm401492x]

6. Murumkar PR, Le L, Truong TN, Yadav MR.  (2011)  Determination of structural requirements of influenza neuraminidase type A inhibitors and binding interaction analysis with the active site of A/H1N1 by 3D-QSAR CoMFA and CoMSIA modeling,  2  (8): [10.1039/C1MD00050K]

7. Xie Y, Xu D, Huang B, Ma X, Qi W, Shi F, Liu X, Zhang Y, Xu W..  (2014)  Discovery of N-substituted oseltamivir derivatives as potent and selective inhibitors of H5N1 influenza neuraminidase.,  57  (20): [PMID:25255388] [10.1021/jm500892k]

8. Albiñana CB, Machara A, Řezáčová P, Pachl P, Konvalinka J, Kožíšek M..  (2016)  Kinetic, thermodynamic and structural analysis of tamiphosphor binding to neuraminidase of H1N1 (2009) pandemic influenza.,  121  [PMID:27236066] [10.1016/j.ejmech.2016.05.016]

9. Hsu PH, Chiu DC, Wu KL, Lee PS, Jan JT, Cheng YE, Tsai KC, Cheng TJ, Fang JM..  (2018)  Acylguanidine derivatives of zanamivir and oseltamivir: Potential orally available prodrugs against influenza viruses.,  154  [PMID:29843102] [10.1016/j.ejmech.2018.05.030]

10. Wang Z, Cheng LP, Zhang XH, Pang W, Li L, Zhao JL..  (2017)  Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors.,  27  (24): [PMID:29141777] [10.1016/j.bmcl.2017.11.003]

11. Hong BT, Cheng YE, Cheng TJ, Fang JM..  (2019)  Boronate, trifluoroborate, sulfone, sulfinate and sulfonate congeners of oseltamivir carboxylic acid: Synthesis and anti-influenza activity.,  163  [PMID:30576902] [10.1016/j.ejmech.2018.12.027]

12. Zhang H,Wang K,Zhu H,Zhao X,Zhao H,Lei Z,Chen B,Yang F,Liu K,Zhang K,Wang J,Tian Y.  (2020)  Discovery of a non-zwitterionic oseltamivir analogue as a potent influenza a neuraminidase inhibitor.,  200  [PMID:32512482] [10.1016/j.ejmech.2020.112423]

Source

Source(1):

• Scientific Literature