52423-89-9

We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the 125I-[MIP-1β] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC50 = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC50 = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.

The present invention relates to compounds of formula (I), or pharmaceutically acceptable derivatives thereof, useful in the treatment of CCR5-related diseases and disorders, for example, useful in the inhibition of HIV replication, the prevention or trea

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We recently described the synthesis and characterization of MDL 105,212, a non peptide tachykinin antagonist with high affinity for NK1 and NK2 receptors. Here we report the synthesis and structure-activity relationships for a series of analogs of MDL 105,212 with regards to: NK1 and NK2 receptor binding affinity, physical-chemical characterization; in vitro absorption potential; in vitro metabolic stability; and efficacy in a capsaicin-challenge conscious guinea pig model after oral administration.

The present invention relates to substituted pyrrolidinyl-3-yl-alkyl-piperidines, their stereoisomers, and pharmaceutically acceptable salts thereof and processes for preparation of the same. The compounds of the present invention are useful in their pharmacological activities such as tachykinin antagonism, especially substance P and neurokinin A antagonism, and the like. Compounds having the property of tachykinin antagonism are indicated for conditions associated with neurogenic inflammation and other diseases described herein.

The invention relates to quaternary basic amides of the formula STR1 in which Ar is an optionally substituted mono-, di-or tricyclic aromatic or heteroaromatic group;T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C 1-C. sub.4, or a C 1-C 5-alkylene group; Ar' is an unsubstituted or mono-or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl; R is hydrogen or a C 1-C. sub.4-alkyl, or a C 1-C 4-ω-alkoxy(C 2-C 4) alkyl, or a C 2-C 4-ω-alkanoyloxy (C 1-C 4)alkyl;.Q is hydrogen;or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group;Am ⊕ is the radical STR2 in which X 1, X 2 and X 3, together with the nitrogen atom to which they are bonded, form a 1-AZONIABICYCLO[2.2.1] HEPTANE optionally substituted by a phenyl or benzyl group; and A . crclbar. is a pharmaceutically acceptable anion. These compounds are useful for the preparation of drugs intended for the treatment of pathological conditions involving the tachykinin system.

We have synthesized and identified MDL 105,212, a non-peptide tachykinin receptor antagonist that has high affinity for human NK1 ((IC50 = 3.11 nM) and NK2 (IC50 = 8.40 nM) receptors. The chemical synthesis of M

The invention relates to quaternary basic amides of the formula STR1 in which Ar is an optionally substituted mono-, di-or tri-cyclic aromatic or heteroaromatic group;T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C 1-C. sub.4, or a C 1-C 5-alkylene group; Ar' is an unsubstituted or mono-or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl; R is hydrogen or a C 1-C 4-alkyl, or a ω-C 1-C. sub.4-alkoxy(C 2-C 4) alkyl, or a ω-C 2-C. sub.4-alkanoyloxy (C 1-C 4)alkyl;.Q is hydrogen;or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group;Am ⊕ is the radical STR2 in which X 1, X 2 and X 3, together with the nitrogen atom to which they are bonded, form an azabicyclic or azatricyclic system optionally substituted by a phenyl or benzyl group; andA ? is a pharmaceutically acceptable anion.These compounds are useful for the preparation of drugs intended for the treatment of pathological conditions involving the tachykinin system.