Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Bioorg Med Chem Lett ; 17(7): 1883-7, 2007 Apr 01.
Article in English | MEDLINE | ID: mdl-17314043

ABSTRACT

The guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde, 1, with an IC(50) of 840 nM against the CCR5 receptor was identified using high-throughput screening. Optimization efforts led to the discovery of a novel piperidine series of CCR5 antagonists. In particular, the 4-hydroxypiperidine derivative, 6k, had improved potency against CCR5, and was a starting point for further optimization. SAR elaboration using parallel synthesis led to the identification of 10h, a potent CCR5 antagonist with an IC(50) of 11 nM.


Subject(s)
CCR5 Receptor Antagonists , Chemistry, Pharmaceutical/methods , Piperidines/chemistry , Animals , Cell Line , Drug Design , Humans , Inhibitory Concentration 50 , Models, Chemical , Molecular Conformation , Molecular Structure , Piperidines/chemical synthesis , Piperidines/pharmacology , Rats , Structure-Activity Relationship , Time Factors , Transfection
2.
Bioorg Med Chem Lett ; 17(1): 231-4, 2007 Jan 01.
Article in English | MEDLINE | ID: mdl-17081751

ABSTRACT

High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.


Subject(s)
Anti-HIV Agents/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemistry , CCR5 Receptor Antagonists , Mitoguazone/analogs & derivatives , Anti-HIV Agents/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Cells, Cultured , Drug Evaluation, Preclinical , Humans , Inhibitory Concentration 50 , Structure-Activity Relationship
3.
Bioorg Med Chem Lett ; 14(3): 761-5, 2004 Feb 09.
Article in English | MEDLINE | ID: mdl-14741285

ABSTRACT

Compound 2 was identified by high throughput screening as a novel PAI-1 inhibitor. Systematic optimization of the A, B, and C segments of 2 resulted in the identification of a more potent compound 39 with good oral bioavailability. The synthesis and SAR data are presented in this report.


Subject(s)
Piperazines/chemical synthesis , Piperazines/pharmacology , Plasminogen Activator Inhibitor 1/chemistry , Animals , Blood Coagulation Tests , Drug Evaluation, Preclinical , Fibrinolysis/drug effects , Molecular Structure , Plasminogen Activator Inhibitor 1/metabolism , Rats , Structure-Activity Relationship
4.
J Org Chem ; 62(24): 8400-8405, 1997 Nov 28.
Article in English | MEDLINE | ID: mdl-11671978

ABSTRACT

Tricolorin A (1), a structurally amazing resin glycoside with promising bioactivities from Ipomoea tricolor cav. (convolvulaceae), was synthesized in a total of 45 steps, with the longest linear sequence of 20 steps and overall yield of 0.65% from D-mannitol. The AB disaccharide 19-membered lactone 2 was constructured by a regioselective macrolactonization using Corey-Nicolaou protocol. The macrolactone tetrasaccharide 33 was realized either by "one-pot two-step" glycosylation procedure or by a stepwise assembly employing the "armed-disarmed" glycosylation strategy.

SELECTION OF CITATIONS
SEARCH DETAIL
...