Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C32H42N6O3 |
| Molecular Weight | 558.7143 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=CC=C(CCCO)C(NCC2=CC=C3N=C(NCCCN4CCOCC4)N(CC5=NC(C)=CC=C5O)C3=C2)=C1
InChI
InChIKey=DKORMNNYNRPTBJ-UHFFFAOYSA-N
InChI=1S/C32H42N6O3/c1-23-6-9-26(5-3-16-39)28(19-23)34-21-25-8-10-27-30(20-25)38(22-29-31(40)11-7-24(2)35-29)32(36-27)33-12-4-13-37-14-17-41-18-15-37/h6-11,19-20,34,39-40H,3-5,12-18,21-22H2,1-2H3,(H,33,36)
| Molecular Formula | C32H42N6O3 |
| Molecular Weight | 558.7143 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
TMC-353121, a small substituted benzimidazole RSV fusion inhibitor, has been developed by molecular modeling of the precursor molecule JNJ-2408068. It maintains high activity (pEC50 9.9) and low cytotoxicity, while presenting a shorter half-life in the lung (lung t1/2 25 h). TMC-353121 binds to an intermediate conformation of F. Binding of TMC353121 stabilizes the interaction of HR1 and HR2 in an alternate conformation of the 6HB, in which direct binding interactions are formed between TMC-353121 and both HR1 and HR2. Rather than completely preventing 6HB formation, data indicate that TMC-353121 inhibits fusion by causing a local disturbance of the natural 6HB conformation. TMC-353121 is a novel potent antiviral drug, in vivo reducing RSV replication and inhibiting consequential lung inflammation, with a great potential for further clinical development.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121). | 2008 Feb 28 |
|
| Prospects for the development of fusion inhibitors to treat human respiratory syncytial virus infection. | 2009 Jul |
Sample Use Guides
African green monkeys: Study 1. Study 1 evaluated the prophylactic and therapeutic efficacy of a CI of TMC-353121 at a target plasma level of 50 ng/mL. Total of 15 animals were divided into 3
groups- Group 1: the prophylactic arm (Px50), received a 0.033 mg TMC353121/mL solution at a flow rate of 2.5 mL/kg/h, starting 24 hours before infection daily, for a total duration of 10 days; Group 2: the therapeutic arm (Tx50), received the same dose, starting 24 hours postinfection, for a total duration of 8 days; Group 3: the control arm (Vh1), received the vehicle (4% aqueous Captisol), starting 24 hours after infection, for a total duration of 8 days.
Study 2. Study 2 evaluated the prophylactic efficacy of a CI of TMC-353121 at target plasma levels of 5 and 500 ng/mL. Total of 12 animals were divided into 3 groups Group 1: the Prophylactic 5 arm (Px5), received a solution of 0.0033 mg/mL TMC-353121, at a
flow rate of 2.5 mL/kg/h, starting 72 hours before infection, for a total duration of 16 days;
Group 2: the Prophylactic 500 arm (Px500) received 0.33 mg/mL TMC-353121; Group 3: the control arm (Vh2) received vehicle (4% aqueous Captisol) during the same time span
Route of Administration:
Intravenous
| Substance Class |
Chemical
Created
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Edited
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| Record UNII |
538EBT31Z1
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| Record Status |
Validated (UNII)
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