Abstract: Process and novel intermediates for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol ganciclovir) and its pharmaceutically acceptable salts. The present process and monoester intermediates provide for mono-esterification by an L-valine derivative, resulting in a monocarboxylate-monovalinate which is then selectively hydrolyzed under basic or enzymatic conditions to give the monovaline ester of ganciclovir in high yield and purity. These products are of value as antiviral agents with improved absorption.

Abstract: This invention relates to a human stromelysin-1 (i.e., HSL-1) promoter and uses therefor. In particular, the invention provides a purified DNA containing a functional HSL-1 promoter region that corresponds in structure to the native genomic form of this promoter, an expression vector containing a portion of the purified promoter DNA operatively linked to a heterologous DNA sequence encoding a detectable gene product, a host cell transformed with this factor , a pharmacologic screening assay for stromelysin-1 promoter modulating activity, and a method of modulating TNF .alpha. level and matrix metalloproteinase activities in inflamed tissues of a mammal.

Abstract: Synthetic polypeptide analogs of parathyroid hormone PTH, parathyroid hormone related peptide PTHrp, and of the physiologically active truncated homologs and analogs of PTH and PTHrp, in which amino acid residues (22-31) form an amphipathic .alpha.-helix, said residues (22-31) selected from hydrophilic amino acids (Haa) and lipophilic amino acids (Laa) ordered in the sequence:Haa(Laa Laa Haa Haa).sub.2 Laaand their pharmaceutically acceptable salts are useful for the prophylaxis and treatment of corticosteroid induced osteopenia in mammals.

Abstract: Synthetic polypeptide analogs of parathyroid hormone PTH, parathyroid hormone related peptide PTHrp, and of the physiologically active truncated homologs and analogs of PTH and PTHrp, in which amino acid residues (22-31) form an amphipathic .alpha.-helix, said residues (22-31) selected from hydrophilic amino acids (Haa) and lipophilic amino acids (Laa) ordered in the sequence:Haa(Laa Laa Haa Haa).sub.2 Laaand their pharmaceutically acceptable salts are useful for the prophylaxis and treatment of ostoporosis in mammals. Processes for the production of the polypeptides via solid phase and recombinant methods are provided.

Abstract: Synthetic polypeptide analogs of parathyroid hormone PTH, parathyroid hormone related peptide PTHrp, and of the physiologically active truncated homologs and analogs of PTH and PTHrp, in which amino acid residues (22-31) form an amphipathic .alpha.-helix, said residues (22-31) selected from hydrophilic amino acids (Haa) and lipophilic amino acids (Laa) ordered in the sequence:Haa(Laa Laa Haa Haa).sub.2 Laaand their pharmaceutically acceptable salts are useful for the prophylaxis and treatment of ostoporosis in mammals. Processes for the production of the polypeptides via solid phase and recombinant methods are provided.

Abstract: One aspect of the present invention is a purified human GMP synthetase and a method of purifying it from naturally occurring sources. Another aspect of the present invention is a recombinant human GMP synthetase as well as DNA sequences coding for human GMP synthetase, expression vectors comprising such a coding sequence, and host cells transformed with these expression vectors capable of producing human GMP synthetase. Also forming part of this invention is a recombinant process for the production of GMP synthetase. Further provided is a method of purifying GMP synthetase from natural or recombinant sources. Other aspects of the invention include antibodies to human GMP synthetase and the use of such antibodies to assay for human GMP synthetase. Another aspect of this invention is the use of purified naturally occurring human GMP synthetase or recombinant human GMP synthetase to identify inhibitors of GMP synthetase activity.

Abstract: Compounds having immunomodulatory activity comprising the optionally modified dodecapeptide fragment A-(SEQ ID No: 1)-B corresponding to residues 174 to 185 of C-reactive protein (CRP), pharmaceutical compositions thereof, and methods of treating cancer with the compositions. Liposomal formulations containing the CRP-peptide fragment are particularly efficacious when administered in conjunction with interleukin-2.

Abstract: Compounds of formula (I): ##STR1## as single stereoisomers or mixtures thereof and their pharmaceutically acceptable salts inhibit matrix metalloproteases, such as interstitial collagenases, and are useful in the treatment of mammals having disease states alleviated by the inhibition of such matrix metalloproteases, for example arthritic diseases or bone resorption diseases, such as osteoporosis.

Abstract: Synthetic nona- and decapeptide LHRH antagonist analogs are disclosed, having a sterically hindered guanidino-substituted arginyl or homoarginyl residue at position 8, with no arginyl substituent at position 6.

Abstract: The present invention relates to novel 5-HT.sub.4 receptor ligands which are 1-(5-halo-4-aminophenyl) (C.sub.2-6)alkan-1-one derivatives in which the 5-halo-4-aminophenyl group is substituted at its 2-position with (C.sub.1-4)alkyloxy or phenyl(C.sub.1-4)alkyloxy and optionally substituted at its 3-position with (C.sub.1-4)alkyloxy or substituted at its 2- and 3-positions together with methylenedioxy or ethylenedioxy and the highest numbered carbon of the (C.sub.2-6)alkan-1-one is substituted with di(C.sub.1-4)alkylamino, morpholin-1-yl or pyrrolidin-1-yl or optionally substituted piperidin-1-yl, piperidin-4-yl, azacyclohept-1-yl, azabicyclo?2.2.1!hept-3-yl, azabicylo?2.2.2!oct-3-yl or azabicylo?3.2.2!non-3-yl; and the pharmaceutically acceptable salts, individual isomers and mixtures of isomers and methods of using and making such derivatives.

Abstract: This invention provides a sustained release composition comprising a PLGA matrix, a bioactive agent, and a quaternary ammonium surfactant, in which the release profile of the bioactive agent from the PLGA matrix is controlled by the concentration of the quaternary ammonium surfactant.

Abstract: Process for preparing the L-monovaline ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol and its pharmaceutically acceptable salts. The present process provides an N,O-bis-trityl intermediate of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol which allows for mono-esterification by an L-valine derivative. These products are of value as antiviral agents with improved absorption.

Abstract: The disclosed pyrimidine derivatives, and pharmaceutically acceptable salts thereof, exhibit useful pharmacological properties, in particular use as 5HT.sub.2C - antagonists. The invention is also directed to formulations and methods for treatment.

Abstract: This invention provides a vector for expression of a nucleic acid cassette in bronchial epithelial and vascular endothelial cells comprising a segment of the 5'-flanking region of the preproendothelin-1 gene, upstream from the transcription start site, the first exon of the preproendothelin-1 gene, and a nucleic acid cassette, wherein the nucleic acid cassette is located within the first exon, in sequential and positional relationship for expression of the nucleic acid cassette.

Abstract: Heterocyclic compounds of Formula I: ##STR1## in which n is 2, 3, 4, 5 or 6; t is 1, 2, 3 or 4; u is 0 or 1 (provided that t is not 1 when u is 0); X is O or N(R.sup.4); Y and Z are independently C(O), C(S) or CH.sub.2 (provided that Y and Z are not both CH.sub.2); R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined in the specification; and their pharmaceutically acceptable salts and N-oxides, formulations containing them, their uses as therapeutic agents, and their synthesis.

Abstract: Compounds of the Formula: ##STR1## wherein: R.sup.1 and R.sup.2 are independently hydrogen or lower alkyl;R.sup.3 is hydrogen, lower alkyl, lower alkoxy, hydroxy, halo, optionally substituted phenyl, amino, nitro or trifluoromethyl; andX is --NH--, --O-- or --S--;and the pharmaceutically acceptable salts thereof exhibit high affinity and selectivity for imidazoline receptors, and are are particularly useful for modification of the female reproductive cycle.

Abstract: Compounds represented by the Formula I: ##STR1## wherein: R.sup.1 is hydrogen or lower alkyl;R.sup.2 is heteroaryl; andR.sup.3 and R.sup.4 are independently hydrogen or lower alkyl;and the pharmaceutically acceptable salts thereof, are useful as chemotherapeutic agents.

Abstract: The present invention relates to novel benzocycloalkylazolethione compounds which are dopamine .beta.-hydroxylase inhibitors in which the benzocycloalkyl portion of the compound is selected from indanyl, 1,2,3,4-tetrahydronaphthalenyl and 6,7,8,9-tetrahydro-5H-benzocycloheptenyl (in which the benzo is optionally substituted with one to three substituents) and the azolethione portion of the compound is selected from 2-thioxo-2,3-dihydro-1H-imidazol-3-yl, 5-thioxo-4,5-dihydro-1H-?1,2,4!triazol-4-yl and 5-thioxo-4,5-dihydro-1H-?1,2,4!triazol-1-yl (each optionally substituted with one to three substituents); and the prodrugs, pharmaceutically acceptable salts, individual isomers and mixtures of isomers and the methods of using and preparing such benzocycloalkylazolethione compounds.

Abstract: Benzo or pyridopyridazinones and pyridazinthiones of the formula ##STR1## wherein: X and Y are nitrogen or carbon, provided that at least one is carbon, and Z is oxygen or sulfur;R.sup.1 is hydrogen, lower alkyl, aryl, aralkyl, heterocyclo, heterocyclo lower-alkyl, heteroaryl, or heteroaralkyl;R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently selected from hydrogen, lower alkyl, halo, carboxy, alkoxycarbonyl, carbamoyl, lower-alkyl carbonyl, halocarbonyl, thiomethyl, trifluoromethyl, cyano or nitro;or a pharmaceutically acceptable ester, ether or salt thereof, have been found to be useful as an anti-inflammatory, antasthmatic, immunosuppressive, anti-allograft rejection, anti-graft-vs-host rejection, autoimmune disease or analgetic agent(s).

Abstract: Methods for labeling a material are disclosed. The methods comprise combining with the material (a) a photosensitizer capable upon irradiation of generating singlet oxygen and (b) a chemiluminescent compound capable of being activated by singlet oxygen wherein the photosensitizer and the chemiluminescent compound are incorporated in a particulate matrix or a non-particulate solid matrix. The particulate matrix can be solid or fluid. The methods allow for generating delayed luminescence, which can be realized upon irradiation of the matrix. The methods have application to the determination of an analyte in a medium suspected of containing the analyte.