Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C33H44N4O6S |
| Molecular Weight | 624.791 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC(=O)N[C@@H](C(C1=CC=CC=C1)C2=CC=CC=C2)C(=O)NCCCC[C@@H](CO)N(CC(C)C)S(=O)(=O)C3=CC=C(N)C=C3
InChI
InChIKey=QAHLFXYLXBBCPS-IZEXYCQBSA-N
InChI=1S/C33H44N4O6S/c1-24(2)22-37(44(41,42)29-19-17-27(34)18-20-29)28(23-38)16-10-11-21-35-32(39)31(36-33(40)43-3)30(25-12-6-4-7-13-25)26-14-8-5-9-15-26/h4-9,12-15,17-20,24,28,30-31,38H,10-11,16,21-23,34H2,1-3H3,(H,35,39)(H,36,40)/t28-,31-/m0/s1
| Molecular Formula | C33H44N4O6S |
| Molecular Weight | 624.791 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
MX-100 (also known as PL-100) is a benzenesulfonamide derivative patented by Pharmacor Inc as HIV aspartyl protease inhibitor. MX-100 retained excellent antiviral activity against almost all of these protease inhibitor-resistant viruses and that its performance in this regard was superior to those of atazanavir, amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir. In almost every case, the increase in the EC50 for MX-100 observed with viruses containing multiple mutations in protease was far less than that obtained with the other drugs. Preclinical studies showed that MX-100 possessed suboptimal solubility and pharmacokinetic, (PK) properties, possibly hindering further development. MX-100 successfully completed preclinical and clinical development (phase I in healthy volunteers) and have been licensed to Merck in 2006
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Lysine sulfonamides as novel HIV-protease inhibitors: Nepsilon-acyl aromatic alpha-amino acids. | 2006 Jul 1 |
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| Epsilon substituted lysinol derivatives as HIV-1 protease inhibitors. | 2010 Jul 15 |
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| Assessment of the susceptibility of mutant HIV-1 to antiviral agents. | 2010 May |
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| In vitro and structural evaluation of PL-100 as a potential second-generation HIV-1 protease inhibitor. | 2013 Jan |
| Substance Class |
Chemical
Created
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JRI5GOF0K0
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ACTIVE MOIETY |
In the present study, we compared the antiviral activity of PL-100 against HIV-1 subtype B with that of darunavir. We used tissue culture experiments to evaluate the in vitro development of resistance to PL-100 and tested the antiviral activity of several clinically approved PIs against PL-100-selected resistant variants. Structural modelling was also used to compare the binding of PL-100 and darunavir to the HIV-1 protease (PR) enzyme.PL-100-resistant variants that emerged within 8-48 weeks showed low- to high-level resistance (3.5- to 21.6-fold) to PL-100, but commonly retained susceptibility to darunavir, which, in contrast, did not select for resistance mutations over a period of 40 weeks. Hydrogen-bonding contacts and the di-THF group in darunavir, as well as the hydrophobic nature of PL-100, contribute to PI binding and a high genetic barrier for resistance. Redesigning the structure of PL-100 to include a di-THF group might improve it.
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ACTIVE MOIETY |
A selection for resistance against PL-100 in cord blood mononuclear cells was performed, using the laboratory-adapted IIIb strain of HIV-1, and it was shown that resistance appears to develop slower against this compound than against amprenavir, which was studied as a control. Four mutations in protease (PR) were selected after 25 weeks: two flap mutations (K45R and M46I) and two novel active site mutations (T80I and P81S).
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ACTIVE MOIETY |
Class: Aniline compound, Antiretroviral, Benzhydryl compound, Carbamate, Phosphoric acid ester, Small molecule, Sulfonamide; Mechanism of Action: HIV protease inhibitor; Highest Development Phase: Preclinical for HIV infection; Most Recent Events: 20 May 2016 PPl 100 (SC, IM) is still in preclinical development for HIV infections in Taiwan, 09 Jul 2013 No development reported - Phase-I for HIV infections in Canada (PO)
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