The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V):

##STR00001##

or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R.sup.3, R.sup.4, R.sup.6, R.sup.11, X.sup.1, X.sup.2, and X.sup.3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): ##STR00001##
or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R.sup.3, R.sup.4, R.sup.6, R.sup.11, X.sup.1, X.sup.2, and X.sup.3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): ##STR00001##
or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R.sup.3, R.sup.4, R.sup.6, R.sup.11, X.sup.1, X.sup.2, and X.sup.3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

Spirocyclic compounds, including chiral spiro diamine, chiral spiro amino naphthol, chiral spiro bis(indole), chiral spiro diaryl diol, chiral spiro diaryl diamine, chiral spiro amino naphthol, chiral spiro diaryl diindole, and chiral spiro phospholane useful as chiral ligands and chiral organocatalysts and methods of preparation and methods of use thereof. Owing to the molecular shape and three-dimensional orientation, the chiral diamine and chiral amino naphthol molecules provide a skeleton for use as ligands and organocatalysts.

Spirocyclic compounds, including chiral spiro diamine, chiral spiro amino naphthol, chiral spiro bis(indole), chiral spiro diaryl diol, chiral spiro diaryl diamine, chiral spiro amino naphthol, chiral spiro diaryl diindole, and chiral spiro phospholane useful as chiral ligands and chiral organocatalysts and methods of preparation and methods of use thereof. Owing to the molecular shape and three-dimensional orientation, the chiral diamine and chiral amino naphthol molecules provide a skeleton for use as ligands and organocatalysts.

A palladium(II) complex which catalyzes the Sonogashira coupling reaction efficiently under aerobic condition and a method of employing the palladium(II) complex to synthesize internal alkynes. The palladium(II) complex is an effective catalyst for the coupling reactions of aryl iodo and diiodo compounds with unactivated alkyl alkynes and terminal dialkynes to produce various novel symmetrical dialkynes and disubstituted internal alkynes in excellent yields.

The invention provides for methods for the synthesis of various compounds through reaction of carboxamide, or carboxamide derivatives, with various substituted or unsubstituted haloalkanols in a one-step, single vessel, reaction mechanism. Preferably, but not exclusively, the reaction proceeds in the absence of any solvents, catalyst, base, or any further reagents.

The invention provides for methods for the synthesis of various compounds through reaction of carboxamide, or carboxamide derivatives, with various substituted or unsubstituted haloalkanols in a one-step, single vessel, reaction mechanism. Preferably, but not exclusively, the reaction proceeds in the absence of any solvents, catalyst, base, or any further reagents.