Abstract: The present invention provides novel HIV protease inhibitors, pharmaceutical formulations containing those compounds and methods of treating HIV infection.

Abstract: Pharmaceutical compounds as follows:9,10-dihydro-9,10-dioxo-4,5,8-trimethoxyanthracene-2-carboxylic acid,4,5-diethoxy-9,10-dihydro-9,10-dioxoanthracene-2-carboxylic acid,9,10-dihydro-9,10-dioxo-4,5-dipropoxyanthracene-2-carboxylic acid,4,5-dibutoxy-9,10-dihydro-9,10-dioxoanthracene-2-carboxylic acid,9,10-dihydro-5,8-dimethoxy-9,10-dioxoanthracene-2-carboxylic acid,7-acetoxy-9,10-dihydro-9,10-dioxoanthracene-2-carboxylic acid;and salts and esters thereof.

Abstract: Thrombin inhibitors represented by the formula ##STR1## as provided wherein A(C.dbd.O)-- is, inter alia, phenylglycyl, cyclohexylglycyl, cyclohexenylglycyl, thienylglycyl or naphthylglycyl, wherein the .alpha.-amino group is preferably substituted by alkyl e.g. methyl or an alkoxycarbonyl, cycloalkoxycarbonyl or arylkoxycarbonyl group e.g. t-butyloxycarbonyl. A(C.dbd.O)-- also represents an .alpha.-substituted acetyl group such as .alpha.-methoxyphenylacetyl; or a bicyclic group such as a tetrahydroisoquinolin-1- or 3-carbonyl group; a perhydroisoquinolin -1- or -3-carbonyl group; or a 1-amino or (substituted amino) cycloalkylcarbonyl group such as 1-aminocyclohexylcarbonyl. Also provided are a method for inhibiting the formation of blood clots in man and animals by administering a thrombin inhibitor of the above formula and pharmaceutical formulations useful in the method.

Abstract: Processes for preparing 2,2-difluoroketene silyl O,S-acetals and .alpha.,.alpha.-difluoro-.beta.-silyloxy-1,3-dioxolane-4-propanoic acid O,S-esters.

Abstract: Pharmaceutical compounds of the formula: ##STR1## R.sup.1 to R.sup.8 are each hydrogen or C.sub.1-4 alkyl, m, n and p are each 0, 1, or 2, q is 0, 1, 2 or 3, X and Z are each C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxy, nitro, cyano, halo, trihalomethyl, carboxy, C.sub.1-4 alkoxy-carbonyl or phenyl, and in addition z, together with the phenyl ring to which it is attached, can be: ##STR2## Y is --O--, --S-- or --CH.sub.2 --, V is --(CH.sub.2).sub.r -- or --(CH.sub.2).sub.r S-- where r is 1 to 15, and W is hydrogen or optionally substituted phenyl; and salts thereof.

Abstract: The present invention provides a novel method of lowering serum cholesterol in humans comprising ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different provided that, when R.sup.1 and R.sup.2 are the same, each is a methyl or ethyl group, and, when R.sup.1 and R.sup.2 are different, one of them is a methyl or ethyl group and the other is a benzyl group, or a pharmaceutically acceptable salt thereof.

Abstract: A method for selectively deactivating catalase while retaining D-amino acid oxidase activity is disclosed. The catalase and the oxidase are both present in whole cells or a cell-free extract. The method comprises combining the whole cells or the cell-free extract with a basic solution at a pH between about 11 and about 12 for a time of about 1 hour and 45 minutes to about 2 hours. The catalase activity is eliminated and the oxidase activity is uneffected. This results in the production of a solution which contains the oxidase and which has no catalase activity. The pH of the solution containing the oxidase is then lowered to provide a D-amino acid oxidase capable of enzymatic oxidation of cephalosporin C to glutaryl-7-ACA in high yields. The whole cells and cell-free extract are preferrably from Triginopsis variablilis.

Abstract: A method is disclosed for the rapid synthesis of very large numbers of peptides which can be integrated with the screening of these peptides as heterogeneous mixtures to identify the specific peptides which demonstrate biological activity using a small number of coupling steps.

Abstract: A group of 2-amino-3-aroyl-benzo[.beta.]thiophenes are prepared by preparing an .alpha.-hydroxy thioacetamide by silyl mediated condensation of an aldehyde with an anion of dialkylamino thioformamide, cyclizing the .alpha.-hydroxy thioamide, and subsequently acylating the benzo[.beta.]thiophene to yield the 2-amino-3-aryl derivative. These compounds may be treated with suitable phenyl Grignard reagents, and after deprotection, yield 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[.beta .]thiophene.

Abstract: A method of inhibiting cartilage degradation comprising administering to a human or other mammal in need of treatment an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidino and piperidino, a pharmaceutically acceptable salt or solvate thereof.

Abstract: Thrombin inhibitors represented by the formula ##STR1## as provided wherein A is e.g. phenylglycyl, and phenylalanyl, .alpha.-methylphenylalanine and .alpha.-methylphenylglycine wherein the amino group is preferably substituted with lower alkyl alkanoyl or lower alkoxycarbonyl, or a bicyclo group e.g. 1,2,3,4-tetrahydroisoquinolin-1-yl or -3-yl and perhydroisoquinolin-1-yl or -3-yl. Also provided are a method for inhibiting clot formation in man and animals, pharmaceutical formulations useful in the method and intermediates for the inhibitors.

Abstract: The invention provides complexes of the formula: ##STR1## wherein X is chloro, hydrogen, vinyl, or --CH.sub.3,Z is O;is 0-5;Y is phenyl or 1,4-cyclohexadien-1-yl;R.sub.1 and R.sub.2 are hydrogen or hydroxy, with the proviso that R.sub.1 and R.sub.2 are not both hydrogen andR.sub.3 is --COO.sup.-, --COO(C.sub.1 -C.sub.4 alkyl), --NO.sub.2 or ##STR2## wherein R.sub.4 is C.sub.1 -C.sub.4 alkyl.

Abstract: The present invention provides novel methods of lowering serum cholesterol and inhibiting smoother muscle cell proliferation, particularly restenosis, in humans, and inhibiting uterine fibroid disease and endometriosis in women comprising administering to a human/woman in need of treatment an effective amount of a compound of formula I ##STR1## wherein R is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, halo, or trifluoromethyl;R.sup.1 and R.sup.2 each are the same or different C.sub.1 -C.sub.6 alkyl group;n is an integer from 2 to 6; andR.sup.3 and R.sup.4 each are independently C.sub.1 -C.sub.4 alkyl, or combine to form a substituent selected from the group consisting of pyrrolidino, morpholino, piperidino, piperazino, 4-(C.sub.1 -C.sub.6 allkyl)piperazino, and 4-phenyl-piperazino; or a pharmaceutically acceptable salt thereof.

Abstract: A method of inhibiting bone loss comprising administering to an animal an effective amount of a compound having the formula ##STR1## wherein: R.sup.1 and R.sup.2 are, independently, --H, --OH, halo, --OC.sub.1 -C.sub.17 alkyl, --OC.sub.3 -C.sub.6 cycloalkyl, --O(CO)C.sub.1 -C.sub.17 alkyl, --O(CO) aryl, --O(CO)O aryl, or --OSO.sub.2 -(n-butyl or n-pentyl);R.sup.3 is ##STR2## R.sup.4 is --H, methyl, ethyl, propyl, ethenyl or ethynyl; or a pharmaceutically acceptable salt or solvate thereof.

Abstract: The invention is directed to the crystalline isopropyl alcohol solvate of loracarbef, and also is directed to a process for the preparation of the crystalline monohydrate form of the compound of formula (I) ##STR1## which includes exposing the crystalline isopropyl solvate form of the compound of formula (I) to a temperature of between about 50.degree. and 90.degree. C. and a relative humidity of between about 60 to about 100%.

Abstract: The current invention provides methods and pharmaceutical formulations that are useful for inhibiting the loss of bone. These methods and formulations can be used without the associated adverse effects of estrogen therapy, and thus serve as an effective and acceptable treatment for osteoporosis.

Abstract: Novel vectors and methods for a single-stranded DNA mediated gene transfer system via transformation, fusion or transduction of Streptomyces, other actinomycetes, and E. coli using a variety of vectors. Phasmid shuttle vectors of the invention are particularly useful as single-stranded vectors that appear to bypass one or more host cell restriction systems, and thus increase the efficiency of gene transfer into highly restrictive host cell systems. New and useful vectors are provided that allow for the cloning of genes both for increasing the yields of known antibiotics and also for producing new antibiotics, antibiotic derivatives, or any other useful gene product, including a variety of mammalian protein products.

Abstract: New glycopeptide antibiotic A83850, comprising A83850A, and A83850B, is produced by Amycolatopsis albus strain NRRL 18532. A83850A and A83850B can be reduced to give new biologically active denatures. The A83850 antibiotics have activity against Gram-positive bacteria comparable to that of vancomycin.

Abstract: A method of treating peri-menopasual syndrome comprising administering to a human in need of treatment an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Abstract: A novel method of selecting Streptomyces recombinant DNA-containing host cells and vectors useful in the method are described. The vectors confer tylosin resistance to sensitive Streptomyces host cells and thus provide a convenient method of selecting Streptomyces transformants. The novel tylosin resistance-conferring gene described can be isolated on an .about.2.6 kb KpnI restriction fragment from plasmid pSVB2. Plasmid pSVB2 can be isolated from Streptomyces lividans TK23/pSVB2 (NRRL 15880).