HIV replication inhibitors of formula ##STR00001##
N-oxides, pharmaceutically acceptable addition salts, quaternary amines or stereoisomeric forms thereof, wherein -a.sup.1=a.sup.2-a.sup.3=a.sup.4- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—; -b.sup.1=b.sup.2-b.sup.3=b.sup.4- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—; n and m is 0, 1, 2, 3 and in certain cases also 4; R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; optionally substituted C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; R.sup.2 is OH; halo; optionally substituted C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl; substituted carbonyl; carboxyl; CN; nitro; amino; substituted amino; polyhalomethyl; polyhalomethylthio; —S(═O).sub.pR.sup.6; C(═NH)R.sup.6; R.sup.2a is CN; amino; substituted amino; optionally substituted C.sub.1-6alkyl; halo; optionally substituted C.sub.1-6alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R.sup.16; optionally substituted C.sub.1-6alkyloxyC.sub.1-6alkyl; substituted C.sub.2-6alkenyl or C.sub.2-6alkynyl; —C(═N—O—R.sup.8)—C.sub.1-4alkyl; R.sup.7 or —X—R.sup.7; R.sup.3 is CN; amino; C.sub.1-6alkyl; halo; optionally substituted C.sub.1-6alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R.sup.16; substituted C.sub.1-6alkyl; optionally substituted C.sub.1-6alkyloxyC.sub.1-6alkyl; substituted C.sub.2-6alkenyl or C.sub.2-6alkynyl; —C(═N—O—R.sup.8)—C.sub.1-4alkyl; R.sup.7; —X—R.sup.7; R.sup.4 is halo; OH; optionally substituted C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl; C.sub.3-7cycloalkyl; C.sub.1-6alkyloxy; CN; nitro; polyhaloC.sub.1-6alkyl; polyhaloC.sub.1-6alkyloxy; substituted carbonyl; formyl; amino; mono- or di(C.sub.1-4alkyl)amino or R.sup.7; -A-B— is —CR.sup.5═N—, —N═N—, —CH.sub.2—CH.sub.2—, —CS—NH—, —CO—NH—, —CH═CH—;
pharmaceutical compositions comprising these; methods for the preparation of these compounds and compositions; the use of these compounds for the prevention or the treatment of HIV infection.

The present invention provides compositions and methods for the delivery of antivirals to a cell or subject.

Embodiments of calcium channel agonists, as well as methods of making and using the calcium channel agonists, are disclosed. The disclosed calcium channel agonists and corresponding salt forms have a structure according to general formula I: ##STR00001##
wherein each bond depicted as “” is a single bond or a double bond as needed to satisfy valence requirements; Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 independently are nitrogen or carbon; R.sup.1 and R.sup.3 are alkyl; R.sup.2 is alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R.sup.4 is alkyl or hydroxyalkyl.

Embodiments of calcium channel agonists, as well as methods of making and using the calcium channel agonists, are disclosed. The disclosed calcium channel agonists and corresponding salt forms have a structure according to general formula I: ##STR00001##
wherein each bond depicted as “” is a single bond or a double bond as needed to satisfy valence requirements; Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 independently are nitrogen or carbon; R.sup.1 and R.sup.3 are alkyl; R.sup.2 is alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R.sup.4 is alkyl or hydroxyalkyl.

The present disclosure provides methods of preparing carbocyclic nucleosides, in particular, Prurisol™ ((−) cis-[4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate).

The present disclosure provides methods of preparing carbocyclic nucleosides, in particular, Prurisol™ ((−) cis-[4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-hydroxymethyl acetate).

The invention provides compounds and methods of inhibiting a cyclin-dependent kinase, comprising contacting the cyclin-dependent kinase and an effective amount or concentration of a compound of formula (I) wherein variables are as defined herein. Compounds of formula (I) can be highly selective inhibitors of cyclin-dependent kinases such as CDK12/13, relative to other kinases such as casein kinases, such as CK1δ/ε. Compounds can be used in treatment of cancers, such as breast cancer, brain cancer and ovarian cancer. ##STR00001##

Substituted isoquinolinone compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Substituted isoquinolinone compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

The present invention relates to a process for the preparation of amino alcohol derivatives or salts thereof. In particular the present invention relates to process for the preparation of amino alcohol derivatives or salts thereof which may be used as intermediates in the preparation of HIV reverse transcriptase inhibitors, more preferably Carbovir and Abacavir.

The present invention more specifically relates to a process for the preparation of (1S,4R)-4-amino-2-cyclopentene-1-methanol of Formula IIIa.

##STR00001##

The present invention also specifically relates to process for the preparation of Abacavir sulfate of Formula II using compound of Formula IIIa prepared according to the process of the present invention.

##STR00002##