Abstract: A method for handling and dispensing small volumes of liquid, and apparatus for carrying out the method, are disclosed. A small volume of liquid, which is retained within a fluid-dispensing member, is dispensed therefrom by accelerating, and then abruptly decelerating, the member. The abrupt deceleration causes the retained liquid to discharge. The discharged liquid may be directed toward a receiver. A micro volume liquid dispenser for practicing the method includes a plurality of fluid-dispensing members configured for aspiring and retaining a small liquid volume via capillary action. The dispenser further includes an actuator for moving/accelerating the fluid-dispensing members and for stopping/abruptly decelerating the fluid-dispensing members.

Abstract: A positive displacement positioner employs rigid stops and actuators to position a work piece, such as a microtiter plate, in any one of at least three positions. Positioner platforms, each of which is capable of moving a work piece between at least two distinct positions, are nested in order to multiply the number of positions available. For example, a two-position rigid stop positioner platform nested in a four-position rigid stop positioner platform, or a four-position rigid stop positioner platform nested in a two-position rigid stop positioner platform would permit the movement of a work piece to any one of eight distinct positions. A four-position platform nested inside a four-position platform yields sixteen positions, and so on. Each positioner platform preferably has a symmetrical polygonal outline and nested platforms provide displacement along each of the polygon's axes of symmetry. Consequently, a positioner will preferably provide displacement to any one of a number of positions.

Abstract: Combinatorial chemical libraries of the Formula ?S!-C(O)-L'-Z containing biaryl amino acids are disclosed, in which ?S! represents a solid support and -L'-Z is a linker/compound residue. In these libraries, Z is --NR.sup.1 R.sup.2. R.sup.1 is chosen from H, C.sub.1 to C.sub.20 hydrocarbon, heteroaralkyl, heterocycloalkyl, substituted arylalkyl, alkoxyalkyl or alkyl-SO.sub.2 NH-alkyl and R.sup.4 is an acyl or sulfonyl residue. R.sup.2 is chosen from ##STR1## The combinatorial libraries are optionally encoded with tags. The use of these libraries in assays to discover biologically active compounds is also disclosed.

Abstract: A method and apparatus for high-throughput identity confirmation, quantitation and purity determination of a compound of interest in a mixture of compounds is disclosed. According to the method, a chemical mixture, such as may be obtained from a chemical library, is processed to obtain a stream having a time-varying composition, such as by using a high pressure liquid chromatograph. The stream is split into two portions or streams for substantially contemporaneous detection in a compound-identifying device, such as a mass spectrograph, and in a compound-quantitating device, such as an evaporative light scattering detector. A peak in a chromatogram obtained from the compound-quantitating device is identified as the compound of interest by cross-correlation, via elution time, with chromatographic results obtained from the compound-identifying device. Once the peak is identified as corresponding to the compound of interest, the corresponding peak area is used for quantitation and purity determination.

Abstract: A dryer for use with chemical compounds employs controlled vacuum, elevated temperature and dry, inert gas to dry the chemical compounds. The dryer includes a vacuum chamber into which trays containing the compounds are placed. The chamber includes heating elements which elevate the temperature of chemical samples placed within the chamber. Supplying and evacuating manifolds, each with a plurality of orifices for supplying and evacuating dry inert gas, provide a substantially laminar flow of dry inert gas just above the trays of chemical compounds which are to be dried. The laminar gas flow removes the unwanted vapor which tends to form above the tray of chemical compound, thus accelerating the drying process.

Abstract: Cell culture chambers and incubators are operated to grow cells under a wide variety of conditions. Where those conditions result in too rapid evaporation of the well media for low volume wells such as those found in 1536-well plates, a subchamber is provided to increase the local humidity so that media evaporation is controlled to an acceptable level. A local liquid source is provided. That liquid may be water or an isotonic solution matched to the well media for a particular application.

Abstract: Compounds of Formula I ##STR1## are disclosed as inhibitors of plasmepsin and cathepsin D. The compounds are therefore useful to treat diseases such as malaria. In preferred compounds of formula I, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or a substituted piperazinealkanoic acid. Intermediates in the solid phase synthesis of compounds of formula I, in which the compounds are attached to a solid support, are also disclosed.

Abstract: Novel carbonyl piperazinyl and piperidinyl compounds and pharmaceutical compositions are disclosed. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel carbonyl piperazinyl or piperidinyl compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being.

Abstract: A method and apparatus is provided for the generation and representation of chemical libraries. More particularly, a computer-implemented method and apparatus is provided for the generation and representation of combinatorial chemistry libraries.

Abstract: A homogeneous high throughput assay is described which screens compounds for enzyme inhibition, or receptor or other target binding. Inhibition (or binding) by the library compounds causes a change in the amount of an optically detectable label that is bound to suspendable cells or solid supports. The amounts of label bound to individual cells or solid supports are microscopically determined, and compared with the amount of label that is not bound to individual cells or solid supports. The degree of inhibition or binding is determined using this data. Confocal microscopy, and subsequent data analysis, allow the assay to be carried out without any separation step, and provide for high throughput screening of very small assay volumes using very small amounts of test compound.

Abstract: Compounds of Formula I ##STR1## are disclosed as inhibitors of plasmepsin and cathepsin D. The compounds are therefore useful to treat diseases such as malaria. In preferred compounds of formula I, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or a substituted piperazinealkanoic acid. Intermediates in the solid phase synthesis of compounds of formula I, in which the compounds are attached to a solid support, are also disclosed.

Abstract: A lawn assay is described for determining compounds that affect enzyme activity or that bind to target molecules. Compounds to be screened are cleaved, and diffused from solid supports into a colloidal matrix. Enzymatic catalysis or binding to target molecules by the compounds is carried out in the matrix. Active compounds are found by monitoring a photometrically detectable change in a substrate, coenzyme, or cofactor involved in the enzymatic reaction, or in a labeled ligand bound to the target molecule, that produces a zone of activity associated with the compounds.

Abstract: A solid phase synthesis reaction vessel includes a vessel with a first inlet, a second inlet, and an outlet. A first stopcock is disposed within the first inlet and a second stopcock is disposed within the outlet. Solid phase material is prevented from escaping the reaction vessel via the outlet while allowing fluid to flow through the outlet by a frit. In one embodiment, the reaction vessel includes an outer hollow shell surrounding the vessel to allow cooling or heating fluid to flow therein for controlling the temperature in the interior reaction volume. The solid phase synthesis reaction vessel provides for the independent opening and closing of each of the inlets and outlet to provide for various ways of draining the vessel, varying the conditions within the vessel, and/or adding additional materials into the vessel.

Abstract: An apparatus for electronically reading tubular members, such as cylindrical vials, marked with electronically readable encoded information is disclosed. The apparatus is in the form of a jig having a receiving means adapted to receive an electronic identification means, such as a pen-type bar code reader therein. A receptacle within the jig is adapted to receive a tubular member therein and to allow rotation of the tubular member. An electronic identification means may be placed within the receiving means to read information encoded on the tubular member when placed within the receptacle.

Abstract: Combinatorial libraries are disclosed which are represented by Formula I:(T'--L).sub.q --S--C(O)--L'--II' Iwherein:S is a solid support; T'--L-- is an identifier residue; and --L'--II' is a ligand/linker residue. These libraries contain dihydrobenzopyrans of the formula: ##STR1## which interact (i.e., as agonists or antagonists) with .alpha. adrenergic receptors, dopamine receptors, .sigma.-opiate receptors, and K.sup.+ channels and are inhibitors of carbonic anhydrase isozymes. They are useful in the treatment of ocular diseases such as glaucoma.

Abstract: Novel compounds of Formula ##STR1## are disclosed. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering a compound of the above formula to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being.

Abstract: A high throughput chemical synthesis system utilizing cylindrical reaction vessels is disclosed. Reaction vessels are utilized which include a tubular member adapted for placement of electronically readable identifying indicia thereon. The identifying indicia are representative of reaction conditions within the tubular member and of one or more reagents utilized in a reaction within the tubular members. A method of performing chemical synthesis on solid phase reactive material within a plurality of reaction vessels using a plurality of reaction stages resulting in final products and employing identifying indicia representing the reaction stages is also disclosed. The method includes reading the identifying indicia located on the reaction vessels, reacting one or more reagents within the reaction vessels under particular reaction conditions which may be determined by reading the identifying indicia, thereby synthesizing chemical compounds within the reaction vessels.

Abstract: A combinatorial library is disclosed which is represented by Formula ##STR1## wherein: ##STR2## is a solid support; T'-L- is an identifier residue; and -L'-II' is a ligand/linker residue. This library contains hydroxypropylamines of the formula:Aa.sup.1 -Aa.sup.2 -(CH.sub.2 Ar.sup.1)-CH.sub.2 CHOH-CH.sub.2 XR.sup.1IIwherein:Aa.sup.1 and Aa.sup.2 is each an amino acid joined to each other through an amide bond;Ar.sup.1 is an aromatic ring system;--CH.sub.2 Ar.sup.1 is attached to N on Aa.sup.2 ; andR.sup.1 is H, C.sub.1-20 alkyl, alkenyl, alkynyl, aryl, heteroaryl, aryl or heteroaryl fused to a 3- or 4-membered moiety to form a non-aromatic second ring, or substituted C.sub.1-20 alkyl, alkenyl, or alkynyl.

Abstract: A process for preparing t-butyl 4-(hydroxymethyl)-3-nitrobenzoate from t-butyl 4-(acetoxymethyl)-3-nitrobenzoate which comprises reacting t-butyl 4-(acetoxymethyl)-3-nitrobenzoate with hydrazine or hydrazine hydrate in a lower alkanol at 0.degree.-50.degree. C.

Abstract: Compounds of Formula I ##STR1## are disclosed as inhibitors of plasmepsin and cathepsin D. The compounds are therefore useful to treat diseases such as malaria. In preferred compounds of formula I, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or a substituted piperazinealkanoic acid. Intermediates in the solid phase synthesis of compounds of formula I, in which the compounds are attached to a solid support, are also disclosed.