Abstract: The present invention relates to pharmaceutical formulations of activated protein C which also comprises sucrose, sodium chloride and sodium citrate buffer at a pH between about 5.5 and about 6.5. The activated protein C formulations of the present invention are more stable than other formulations of activated protein C and demonstrate fewer degradation products over time.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Abstract: A series of benzoquinolin-3-ones are pharmaceuticals effective in treating conditions consequent on both Type I and Type II 5.alpha.-reductase.

Abstract: The present invention provides methods for reversing multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted indole, benzofuran, benzothiophene, naphthalene, or dihydronaphthalene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted indole, benzofuran, benzothiophene, naphthalene, or dihydronaphthalene in combination with an oncolytic agent.

Abstract: The present invention provides methods for reversing multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted indole, benzofuran, benzothiophene, naphthalene, or dihydronaphthalene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted indole, benzofuran, benzothiophene, naphthalene, or dihydronaphthalene in combination with an oncolytic agent.

Abstract: The present invention provides a method of treatment for patients with a variety of thrombotic disorders including, but not limited to, stroke, venous thrombosis, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, and thrombosis as a result of peripheral vascular surgery. Said treatment is a combination therapy with human aPC and antiplatelet agents including, but not limited to, aspirin (ASA), clopidogrel, ReoPro.RTM. (abciximab), dipyridamole, ticlopidine and IIb/IIIa receptor antagonists. The synergy will result in the ability to reduce the dosages of the agents used in the combination therapy.

Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.

Abstract: A method of treatment for patients with vascular occlusion and thromboembolic disorders including the acquired disease state of thrombotic stroke, by administering activated protein C. The administration of aPC provides a highly selective therapeutic agent with a low potential for causing bleeding complications. The administration of aPC is beneficial in preventing the local extension of the microvascular and macrovascular occluding arterial thrombus, thereby reducing the neurological deficit resulting from the stroke.

Abstract: Drug and multidrug resistant modulators of the formula: ##STR1## where R.sup.1 and R.sup.2 are independently hydrogen or halo; A is --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --CHR.sup.4 --CH.sub.2 --, or --CH.sub.2 --CHR.sup.5 --CHR.sup.6 --CH.sub.2 --, where R.sup.4 is --H, --OH, or acyloxy; one of R.sup.5 or R.sup.6 is --H, --OH, or acyloxy, and the other is --H; R.sup.3 is a polyaryl; and pharmaceutically acceptable salts and solvates thereof, are described and claimed. Use of the new compounds in the preparation of pharmaceutical compositions is described and claimed. In addition, methods for treating drug and multidrug resistance in various diseases using a compound, or pharmaceutically acceptable salt or solvate thereof, of this invention are described and claimed. Also, methods of enhancing oral bioavailability of a drug and methods of enhancing bioavailability of a drug to the brain using a compound, or pharmaceutically acceptable salt or solvate thereof, of this invention are described and claimed.

Abstract: This invention provides novel indenone derivatives, their pharmaceutical formulations and their use for the inhibition of leukocyte adherence to cells.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Abstract: An improved process to make gemcitabine hydrocrhloride, the improvement consisting essentially of making the lactone intermediate, 2-deoxy-2,2-difluoro-D-erythro-pentafuranose-1 ulose-3,5-dibenzoate: ##STR1## from D-erythro-2-Deoxy-2,2-difluoro 4,5-O-(1-ethylpropyl)-idene) pentoic acid tert Butyl ester wherein, the D-erythro-2-deoxy-2,2 difluoro-4,5-O-(1-ethylproyl)-ideno) pentoic acid tert-Butyl ester is prepared by the process of reacting S-tert-butyl difluoroethane thioate with 2,3-O (1-ethylpropylidene)-D-glyceraldehyde, in a solvent and in the presence of a strong base; with the proviso that the process is conducted in the absence of a catalyst and in the absence of a silyl containing compound.

Abstract: This invention provides a process for preparing a compound of formula III ##STR1## wherein R.sup.1 is bromo, iodo or COOR.sup.2 ;R.sup.2 is H, C.sub.1 -C.sub.4 alkyl, phenyl which may be substituted or benzyl; andA is a 5- or 6-membered aromatic residue which may contain up to three hetero atoms and which may optionally be substituted with one or two groups selected from the group consisting of halo, hydroxy, C.sub.1 -C.sub.4 alkyl, and C.sub.1 -C.sub.4 alkoxy; or a salt thereof, which comprises(a) reacting a compound of formula I ##STR2## wherein R is C.sub.1 -C.sub.4 alkyl or phenyl which may be substituted; andR.sup.1, R.sup.2, and A are as defined above;or a salt thereof, with a sulfurization agent;(b) cyclizing the reaction product from step (a) with guanidine; and(c) optionally salifying the reaction product from step (b).

Abstract: The compound 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate is described and claimed.

Abstract: .alpha.,.alpha.-Difluoro-.beta.-hydroxy thiol esters of Formula (III): ##STR1## wherein: R.sup.c and R.sup.d are independently selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, S-tert-butyl difluorothioacet-2-yl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, substituted C.sub.3 -C.sub.8 cycloalkyl, substituted C.sub.3 -C.sub.8 cycloalkenyl, aryl, substituted aryl, C.sub.6 -C.sub.10 fused aromatic rings, and substituted C.sub.6 -C.sub.10 fused aromatic rings; orR.sup.c and R.sup.d together make up a ring selected from the group consisting of C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, substituted C.sub.3 -C.sub.8 cycloalkyl and substituted C.sub.3 -C.sub.8 cycloalkenyl;R.sup.e is selected from the group consisting of C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl, aryl, substituted aryl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, substituted C.sub.3 -C.sub.8 cycloalkyl and substituted C.sub.3 -C.sub.

Abstract: Processes for preparing 5-substituted pyrrolo?2,3-d!pyrimidines which are useful as intermediates for the preparation of pyrrolo?2,3-d!pyrimidine antineoplastic agents or as antineoplastic agents themselves are provided.

Abstract: A stereoselective glycosylation process for preparing beta-anomer enriched 2'-deoxy-2',2'-difluoropurine and triazole nucleosides and 2'-deoxy-2'-fluoropurine and triazole nucleosides which involves reacting an alpha-anomer enriched 2-deoxy-2,2-difluorocarbohydrate or 2-deoxy-2-fluorocarbohydrate with at least a molar equivalent of a nucleobase derivative in a low freezing inert solvent.

Abstract: A process for producing a compound of the formu5la ##STR1## comprising the step of reacting a compound of the formula ##STR2## with a compound of the formula ##STR3## to form a compound of the formula ##STR4## wherein R.sup.2a is selected from the groups recited above for R.sup.2, or R.sup.2a --X-- is a protected hydroxyl group, and Z is a group of formula --Y--R.sub.5 recited above, or a group that can be converted into a group of said formula --Y--R.sup.5. Intermediates of formula IV and composition containing substantially optically pure enantiomers of Formula (I) are included within the scope of the invention.

Abstract: This invention provides a process for preparing gemcitabine hydrochloride which comprises deblocking .beta.-1-(2'-deoxy-2',2'-difluoro-3',5'-di-O-benzoyl-D-ribofuranosyl)-4-am inopyrimidin-2-one with a catalytic amount of an alkylamine in the presence of methanol or ethanol in an environment essentially free of water; treating the resulting solution with hydrochloric acid and an antisolvent; and recovering the resulting solid gemcitabine hydrochloride.

Abstract: A process for the preparation of compounds of the formula: ##STR1## wherein Pg and R are protecting groups and B is a nucleobase. The process uses protected nucleobases to form 2,2'-anhydro nucleosides having the formula ##STR2## which are hydrolyzed to 2'-hydroxy intermediates which are then oxidized to the desired 2'-keto compounds. The compounds and intermediates are useful as antiviral and antitumor agents and as intermediates to 2,2'-anhydro-1-(.beta.-D-arabinofuranosyl)cytosine (anhydro-ara-C) and 1-.beta.-D-arabinofuranosylcytosine (Ara-C).