Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C33H43N3O10S |
| Molecular Weight | 673.774 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]12OCC[C@@]1([H])[C@H](CO2)OC(=O)N[C@@H](CC3=CC=CC=C3)[C@H](O)CN(CC(C)C)S(=O)(=O)C4=CC=C5OC=C(CNC(=O)OCC)C5=C4
InChI
InChIKey=WBFPRQKPFYYTPM-OSXRZYMSSA-N
InChI=1S/C33H43N3O10S/c1-4-42-32(38)34-16-23-19-44-29-11-10-24(15-26(23)29)47(40,41)36(17-21(2)3)18-28(37)27(14-22-8-6-5-7-9-22)35-33(39)46-30-20-45-31-25(30)12-13-43-31/h5-11,15,19,21,25,27-28,30-31,37H,4,12-14,16-18,20H2,1-3H3,(H,34,38)(H,35,39)/t25-,27-,28+,30-,31+/m0/s1
| Molecular Formula | C33H43N3O10S |
| Molecular Weight | 673.774 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Approval Year
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 11:43:46 UTC 2023
by
admin
on
Sat Dec 16 11:43:46 UTC 2023
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| Record UNII |
GFJ69DDT2E
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| Record Status |
Validated (UNII)
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| Record Version |
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869987-71-3
Created by
admin on Sat Dec 16 11:43:46 UTC 2023 , Edited by admin on Sat Dec 16 11:43:46 UTC 2023
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16073974
Created by
admin on Sat Dec 16 11:43:46 UTC 2023 , Edited by admin on Sat Dec 16 11:43:46 UTC 2023
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GFJ69DDT2E
Created by
admin on Sat Dec 16 11:43:46 UTC 2023 , Edited by admin on Sat Dec 16 11:43:46 UTC 2023
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
Summary of Antiviral Activity and Phenotypic Resistance Data:
- SPI-256 is 4-50 fold more potent than reference PIs against WT B & non-B clades: mean IC50 = 0.3 nM (range: 0.2 - 0.4 nM).
- SPI-256 is fully active against viruses that are highly resistant to the majority of reference PIs (groups 4 and 5): mean IC50 = 0.5 nM (range: 0.2 - 0.9 nM).
- SPI-256 retains high potency against worst-case MDR viruses (groups 6 & 7), although efficacy is reduced compared to WT: mean IC50 = 12.9 nM (range: 1.8 - 34 nM).
- SPI-256, like reference PIs, is hypersensitive to the Atazanavir I50L mutation (group 3): mean IC50 <0.1 nM).
- SPI-256, unlike reference PIs, retains wild type potency against viruses that harbor primary mutations in addition to the I50L mutation (group 14): mean IC50 0.2 nM (range: 0.2 - 0.3 nM).
- SPI-256 remains fully active against the NFV mutations, D30N/N88D, that confer cross-resistance to most or all other PIs (group 1): IC50 = 0.2 nM. - Viruses with any of the single primary mutations V82A, F, T
L90M, I84V and N88S remain fully sensitive to SPI-256 (groups 8-12). Viruses with an I50V mutation (group 2) show reduced relative, but high absolute sensitivity to SPI-256 to SPI-256: IC50 <5.0 NM.
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ACTIVE MOIETY |
SPI-256 also exhibited an excellent resistance profile against multidrug resistant (MDR) isolates. In an analysis of 11 worst case scenario MDR isolates (defined as 6 primary PI mutations and FC>50), SPI-256 retained low nanomolar activity against most MDR isolates and mean IC50 at least an order of magnitude lower than that for atazanavir, lopinavir, amprenavir, tipranavir and other reference PIs and was better than or comparable with darunavir.
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ACTIVE MOIETY |
Class: Anti-retroviral, Antiviral; Mechanism of Action: HIV protease inhibitor; Highest Development Phase: Discontinued for HIV infections; Most Recent Events: 29 Oct 2008 Final pharmacokinetic and adverse events data from a phase I trial in HIV infections presented at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy and 46th Annual Meeting of the Infectious Diseases Society of America (ICAAC/IDSA-2008), 30 Jun 2007 Phase-I clinical trials in HIV infections in USA (unspecified route), 28 Feb 2007 Sequoia Pharmaceuticals files an IND with the the US FDA for SPI 256
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