Abstract: The present invention provides cryptophycin compounds of Formula I that are useful in the treatment of neoplasms.

Abstract: The present invention are macrocycles of the formula (IX): 1

Abstract: Macrocyclic module compositions are made from cyclic synthons. The macrocyclic module structures are prepared by stepwise or concerted schemes which couple synthons in a closed ring. The macrocyclic module structures may have a pore of nanometer dimensions.

Abstract: The invention features a new solid supports having at least one amino functionality and a linker bound to the solid support through at least a portion of the amino functional groups. The invention also features solid support bound substrates suitable for use in the formation of macrocycles by a TE domain catalyzed macrocyclization reaction. The invention features methods of making the solid supports and solid support bound substrates of the invention and methods of effecting macrocyclizations of solid support bound substrates. The invention further provides new macrocyclic molecules having one or more peptide domains and one or more polyketide domains in the macrocyclic ring. In another embodiment of the invention, libraries of macrocycles are provided as well as methods of forming libraries of macrocycles from libraries of solid support bound substrates are provided.

Abstract: The present invention covers macrocyclic compounds of formula I active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus. wherein W, R21, R22, R3, R4, D and A are as defined herein, or a pharmaceutically acceptable salts or ester thereof.

Abstract: The invention relates to novel 15-membered 8a- and 9a-lactams from the class of 6-O-methyl-erythromycin A of general formula (I) their pharmaceutically acceptable addition salts with inorganic or organic acids and their hydrates, to intermediates for their preparation, to a process for their preparation, to their pharmaceutically acceptable addition salts with inorganic or organic acids, to their hydrates, to a process for the preparation of pharmaceutical compositions as well as to a use of pharmaceutical compositions for the treatment of bacterial infections.

Abstract: The invention provides compounds of formula as described in the claims, or an optical isomer, diastereomer or enantiomer thereof, or a pharmaceutically-acceptable salt, or biohydrolyzable amide, ester, or imide thereof are useful as inhibitors of metalloproteases. Also disclosed are pharmaceutical compositions and methods of treating diseases, disorders and conditions characterized by metalloprotease activity using these compounds or the pharmaceutical compositions containing them.

Abstract: A method for treating menopausal hot flushes using CGRP antagonists and/or CGRP release inhibitors and the corresponding pharmaceutical compositions containing as active substance one or more CGRP antagonists and/or CGRP release inhibitors, and the preparation thereof.

Abstract: The invention provides novel cryptophycin compounds which can be useful for disrupting the microtubulin system, as antineoplastic agents, antifungal, and for the treatment of cancer. The invention further provides a formulation for administering the novel cryptophycin compounds.

Abstract: The present invention provides antitumor methods, formulations, and compounds comprising a cryptophycin.

Abstract: The present invention describes an isolated macrocycle having the formula: where d is an integer from 0 to about 100; A, B, and each D are the same or different and are selected from the group consisting of each R1 is the same or different and is a bivalent alkylene moiety; each R2 is the same or different and is a bivalent alkylene moiety; and each R3 is the same or different and is selected from the group consisting of a hydrogen atom and an alkyl moiety. Methods for producing these macrocycles are also described. The macrocycles of the present invention can be used as arthropod repellents.

Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

Abstract: Novel derivatives of PF1022 substance, which are cyclodepsipeptides represented by the general formula (I) shown below or their salts are useful as anthelmintic agent for prevention or treatment of parasitic infections.

Abstract: The present invention is directed to a process for the preparation of a compound of formula (X-a): or a pharmaceutically acceptable salt form thereof, wherein: R1 is selected from the group consisting of: C1-5 alkyl substituted with 0-5 R1a, —(CH2)r—C3-10 cycloalkyl substituted with 0-5 R1a, and —(CH2)r-aryl substituted with 0-5 R1a. Compounds of Formula (X-a) are macrocyclic molecules containing anti-succinate residues which inhibit metalloproteinases such as aggrecanase, and the production of tumor necrosis factor (TNF). The anti-succinates are formed by an Ireland Claisen rearrangement of a silyl ketene acetal which proceeds with high stereoselectivity.

Abstract: The present invention relates to 5-membered ring heterocycles of the formula I, 1

Abstract: This invention relates to macrocyclic molecules which inhibit metalloproteinases, including aggrecanase, and the production of tumor necrosis factor (TNF). In particular, the compounds are inhibitors of metalloproteinases involved in tissue degradation and inhibitors of the release of tumor necrosis factor. The present invention also relates to pharmaceutical compositions comprising such compounds and to methods of using these compounds for the treatment of inflammatory diseases.

Abstract: Compounds of the formula: are described which have activity as anti-inflammatory agents. Cyclic disulfide compounds are provided which inhibit of binding of cells to endothelium. Such compounds are useful for treating inflammatory diseases, such as asthma, whose symptoms and/or damage are related to the binding of cell adhesion molecules to integrin expressing cells.

Abstract: This invention provides a process for preparing diastereomerically pure cryptophycin compounds.

Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains.

Abstract: A novel class of macrolides in whichi) positions 2 to 6 inclusive of the macrocyclic ring are provided by a piperidazinyl carboxylic acid residue; and/orii) positions 7 to 9 inclusive of the macrocyclic ring are provided by an aromatic .alpha.-amino acid residue; and/oriii) positions 10 to 12 inclusive of the macrocyclic ring are provided by an aliphatic .alpha.-amino acid residue, preferably comprising two, or especially all three of the characteristic structural features i), ii) and iii), more especially a compound of formula IX ##STR1## is provided having immunosuppressant and antinflammatory properties and protected and ring-open forms thereof.

Abstract: The present invention relates to the new 15-membered ketoazalides from the class of 6-O-methyl-8a-aza-8a-homo-and 6-O-methyl-9a-aza-9a-homoerythromycin A with the general formula (I) ##STR1## wherein A represents NH group and B at the same time represents C.dbd.O group, orA represents C.dbd.O group and B at the same time represents NH group,R.sup.1 represents OH group, L-cladinosyl group of the formula (II) ##STR2## or together with R.sup.2 represents ketone, R.sup.2 represents hydrogen or together with R.sup.1 represents ketone,R.sup.3 represents hydrogen or C.sub.1 -C.sub.4 alkanoyl group,to intermediates and a process for their preparation, to their pharmaceutically acceptable addition salts with inorganic or organic acids, to the process for the preparation of pharmaceutical compositions, as well as to the use of pharmaceutical compositions for treating bacterial infections.

Abstract: This invention provides for pharmaceutical formulations of compounds which are useful as protective agents when administered to patients also receiving antineoplastic drugs. The invention also includes methods of reducing the toxicity of various antineoplastic agents by administering an effective amount of the protective agent to a patient receiving one or more antineoplastic agents. The compounds useful as protective agents have either a sulfhydryl moiety or are reducible disulfides.

Abstract: This invention relates to compounds of the formula ##STR1## and to pharmaceutically acceptable salts thereof. The compounds of formula 1 are potent antibacterial and antiprotozoal agents that may be used to treat various bacterial and protozoal infections and disorders related to such infections. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of treating bacterial and protozoal infections by administering the compounds of formula 1.

Abstract: This invention provides novel bis-indolylmaleimide macrocycle derivatives of the formula: and solvates thereof. The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.

Abstract: Heterocyclic compounds IR.sup.1 --X--L (I)whereL is a cyclic carbamate residue, a lactonoxy residue or a lactam residue,X is an oxygen-containing group ##STR1## where A is a linker, and R.sup.1 is an organic radical or a group L,are used as activators for inorganic peroxy compounds, in particular as cold bleach activators or optical brighteners in detergents, cleaners and bleaches and in disinfectants.

Abstract: Macrocyclic compounds of formula ##STR1## are potent inhibitors of matrix metalloproteinase and are useful in the treatment of diseases in which matrix metalloproteinase play a role. Also disclosed are matrix metalloproteinase inhibiting compositions and a method of inhibiting matrix metalloproteinase in a mammal.

Abstract: The present invention is directed to novel halo-substituted bis-indolemaleimide compounds of the formula: ##STR1## The invention further provides a method of preparing the disclosed compounds and the preparation of pharmaceutical formulation for use in inhibiting Protein Kinase C in mammals.

Abstract: The present invention relates to N-heterocyclic-containing macrocyclic hydroxyethylamine protease inhibitor compounds, compositions and methods for inhibiting retroviral proteases.

Abstract: The present invention relates to the novel antitumor antibiotic designated BMS-199687 and to its preparation. The compound is obtained by culturing a new strain of Actinomadura ferruginea. BMS-199687 demonstrates antitumor activity in standard antitumor animal model systems.

Abstract: The present invention relates to heat-curable, cyclic isocyanate addition productsi) which are the reaction products of a polyisocyanate having two or more isocyanate groups with a compound containing two or more isocyanate-reactive groups andii) in which at least 10% by weight of the reaction products are in the form of cyclic groups containing urea and/or urethane groups.The present invention also relates to a process for the preparation of these cyclic isocyanate addition products and to the products obtained by curing these compositions at elevated temperatures, e.g., coatings, adhesives, molded articles, elastomers and foams.

Abstract: The present invention is directed to a synthetic process for the formation of ecteinascidin compounds and related structures, such as the saframycins. In one particularly preferred embodiment, the present invention provides a synthetic route for the formation of ecteinascidin 743 (1), ##STR1## an exceedingly potent and rare marine-derived antitumor agent which is slated for clinical trials. The process of this invention is enantio- and stereocontrolled, convergent and short. Also disclosed are novel process intermediates, useful not only in the total synthesis of ecteinascidin 743, but also other known ecteinascidin compounds, including derivatives and analogs thereof.

Abstract: A novel and simple method is proposed for the synthetic preparation of an N,N-disubstituted .beta.-ketothioamide compound represented by the general formulaR.sup.1 R.sup.2 N--CS--CH.sub.2 --CO--R.sup.3,in which R.sup.1 and R.sup.2 are each a monovalent hydrocarbon group or each a divalent hydrocarbon group jointly forming a cyclic structure together with the nitrogen atom and R.sup.3 is a hydrogen atom, a monovalent hydrocarbon group or a divalent hydrocarbon group forming a cyclic structure jointly with R.sup.1, R.sup.1 being a divalent hydrocarbon group and R.sup.2 being a monovalent hydrocarbon group. The method comprises:(a) mixing an N,N-disubstituted amide compound represented by the general formulaR.sup.1 R.sup.2 N--CO--R.sup.3,and a bis(trialkylsilyl)thioketene compound represented by the general formula(R.sub.3 Si).sub.2 C.dbd.C.dbd.

Abstract: The present invention relates to the use of cyclic depsipeptides having 12 ring atoms of the general formula (I) ##STR1## in which R.sup.1 and R.sup.4 independently of one another represent hydrogen, straight-chain or branched alkyl, cycloalkyl, aralkyl, aryl, heteroaryl or heteroarylalkyl, each of which is optionally substituted,R.sup.2, R.sup.3, R.sup.5 and R.sup.

Abstract: A process for preparing compounds of the formula ##STR1## wherein X is O or S; n is one or two; m is zero or one; Y is CH.sub.2, O, or S provided that Y is O or S only when m is one; and A is ##STR2## is disclosed. Also disclosed are processes for preparing the corresponding amino intermediates.

Abstract: A process is provided for preparing intermediates of the structure ##STR1## wherein Rpg is preferably .dbd.CHC.sub.6 H.sub.5 ; and P.G. is a protecting group CBZ or BOC, wherein a protected guanylpyrazole is reacted with an azacycloalkyl, azacycloalkenyl or azaheteroalkyl derivative (such as a piperidine derivative) in the presence of a DBU catalyst. The resulting intermediate may be used as a starting material for preparing thrombin inhibitors.

Abstract: Proposed are an N-(.alpha.-acyloxyethyl) compound, e.g., (N-(.alpha.-acetoxyethyl)-2-pyrrolidone, which is a novel compound and can be converted into an industrially very important N-vinyl compound, e.g., N-vinyl-2-pyrrolidone, by a thermal decomposition reaction under relatively mild conditions as well as a method for the preparation of such an N-(.alpha.-acyloxyethyl) compound. The N-(.alpha.-acyloxyethyl) compound can be synthesized in a high yield by the addition reaction of an NH group-containing compound, e.g., 2-pyrrolidone, with a vinyl carboxylate, e.g., vinyl acetate, in the presence of an alkaline compound such as alkali metal hydroxides.

Abstract: A process of preparing a purified crown compound is disclosed which comprises the steps of (a) dissolving a crown compound and a salt in an organic solvent to form a solution of a complex salt of a crown compound; (b) filtering the solution to obtain a filtrate; (c) adding water to the filtrate to produce a precipitate; and (d) filtering out the produced precipitate.

Abstract: This invention provides novel bis-indolemaleimide macrocycle derivatives of the formula: ##STR1## The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.

Abstract: A compound having the following formula: ##STR1## wherein Me represents a methyl group, having an anti-bacterial activity.

Abstract: Pyrimidinyloxy- and triazinyloxy- and pyrimidinylthio- and triazinylthio-butyric acid derivatives of formula I ##STR1## wherein Q is ##STR2## A is hydroxy or a group ##STR3## and the other substituents are as described in patent claim 1, and salts of compounds of formula I, have herbicidal action and are suitable as active ingredients in weed control compositions.

Abstract: Novel piperidine-triazine compounds of the formula (I) useful as light stabilizers, heat stabilizers and antioxidants for organic materials.The meanings of R.sub.1, R.sub.2, R.sub.3, R.sub.4, X.sub.1, X.sub.2, X.sub.3, Y.sub.1, Y.sub.2, M and N are defined in the text.

Abstract: Cyclodextrin catenanes capable of forming inclusion complexes and a method of preparing them are disclosed. The catenanes comprise one or two per-2,6- di-O-alkyl-.beta.-cyclodextrin macrocycles wherein each per-2,6-di-O-alkyl-.beta.-cyclodextrin macrocycle is interpenetrated by another macrocycle. Such modified cyclodextrins may be used for the electrochemical and optical sensing of small organic molecules, especially small aromatic molecules.

Abstract: Compounds characterized generally as benzo-fused oxazocinyl-terminated alkylamino ethynyl alanine amino diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I ##STR1## wherein A is selected from CO and SO.sub.2 ; wherein X is selected from oxygen atom and methylene; wherein B is a benzo-fused oxazocinyl group; wherein R.sub.1 is selected from hydrido, methyl, ethyl, isopropyl and n-propyl; wherein R.sub.2 is phenylmethyl; wherein each of R.sub.3 and R.sub.5 is hydrido; wherein R.sub.4 is selected from ##STR2## wherein v is selected from hydrido and methyl; wherein R.sub.6 is cyclohexylmethyl; wherein R.sub.7 is selected from isobutyl, cyclopropyl and cyclopropylmethyl; wherein q is a number selected from zero through three, inclusive; and wherein n is a number selected from zero through three, inclusive; or a pharmaceutically-acceptable salt thereof.

Abstract: Compounds characterized generally as oxazocinyl/thiazocinyl-terminated alkylamino ethynyl alanine amino diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I ##STR1## wherein A is selected from CO and SO.sub.2 ; wherein X is selected from oxygen atom and methylene; wherein B is a oxazocinyl/thiazocinyl group; wherein R.sub.1 is selected from hydrido, methyl, ethyl, isopropyl and n-propyl; wherein R.sub.2 is phenylmethyl; wherein each of R.sub.3 and R.sub.5 is hydrido; wherein R.sub.4 is selected from--(CH.sub.2).sub.q --C.tbd.C--Vwherein V is selected from hydrido and methyl; wherein R.sub.6 is cyclohexylmethyl; wherein R.sub.7 is selected from isobutyl, cyclopropyl and cyclopropylmethyl; wherein q is a number selected from zero through three, inclusive; and wherein n is a number selected from zero through three, inclusive; or a pharmaceutically-acceptable salt thereof.

Abstract: Polycyclic compounds (I) can be prepared in accordance with the following reaction formula: ##STR1## wherein R.sub.1 -R.sub.8 each represents a hydrogen atom, a hydroxyl group, an alkoxyl group or a substituted or unsubstituted benzyloxy group or neighboring two groups of R.sub.1 -R.sub.

Abstract: Macrocyclic oxamides may be made easily, in good yield and in one step by reacting an oxalic compound, such as oxalic acid or oxalic esters, with a diamine, where the amine groups are separated by at least five atoms. The oxalic compounds may include, but are not limited to such materials as dimethyl oxalate and diethyl oxalate. The diamines may include, but are not limited to such materials as alkylenediamines; polyalkylene glycol diamines; alkyl-bis-(aminoalkyl)amines; imino bis-(alkyl)amines; and N,N' bis-(aminoalkyl)-N,N'-dialkylalkylenediamines and bis-(aminoalkyl)piperazines; and mixtures thereof. The macrocyclic oxamides made by this process may be used to selectively separate metal ions from solution, or complexed together with a metal ion act as a catalyst.

Abstract: Substituted thienopyrans and processes for preparing the thienopyrans are disclosed. The thienopyrans are useful as antihypertensive agents; antianginals are peripheral antivasoconstrictive agents.

Abstract: Disclosed is a metalloporphyrin-ligand complex which includes (a) a meso-tetraphenylporphyrin, (b) a crown ether rigidly attached to the meso-tetraphenylporphyrin by covalent attachment on one side of the porphyrin to two diagonally opposing phenyl groups, (c) a metal bound to the pyrrole nitrogens of the porphyrin, (d) a bridge covalently linking two diagonally opposing phenyl groups on the other side of the porphyrin, effective to hinder .mu.-oxo diner formation, and (e) a ligand having (i) a primary amine which is held noncovalently by the crown ether and (ii) a metal-coordinating atom which is coordinately bound to the metal.In another aspect, the invention includes a water-soluble oxygen carrier. The oxygen carrier includes a meso-.alpha.,.alpha.,.alpha.,.alpha.-tetrakis(o-propanoylamino)phenylporph yrin, in which the 3-carbons of the propanoyl groups are each covalently bound to a quaternary amine, and iron or cobalt is bound to the pyrrole nitrogens of the porphyrin.

Abstract: Compounds of the formula: ##STR1## are disclosed. These compounds inhibit the angiotensinogen-cleaving action of the natural proteolytic enzyme, renin, and are useful in treating, preventing or managing renin-associated hypertension, hyperaldosteronism, congestive heart failure, and glaucoma.

Abstract: Compounds of the formula ##STR1## in which A.sub.1 and A.sub.2 independently of one another are CO--C.sub.1 -C.sub.4 alkyl, COO--C.sub.1 -C.sub.4 alkyl, CO--CF.sub.3, CO--N(R).sub.2 or cyano;A.sub.1 and A.sub.2 together are CO(X).sub.n --C.sub.1 -C.sub.3 alkylene-(X).sub.n CO, CO(X).sub.n --C.sub.1 -C.sub.3 alkylene-(X).sub.n CO which is substituted by C.sub.1 -C.sub.4 alkyl, COOR, CON(R).sub.2, cyano or phenyl, it being possible for the phenyl ring, in turn, to be substituted by halogen, methyl, trifluoromethyl, methoxy, nitro or cyano; CO--N(R)--CO--N(R)--CO;R is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl or C.sub.3 -C.sub.6 alkynyl;X is oxygen, sulfur or N(CH.sub.3);X.sub.1, X.sub.2 and X.sub.3 independently of one another are hydrogen, halogen, methyl, methylthio, methoxy or nitro;n is 0 or 1;including the salts of the compounds of the formula I with agriculturally acceptable organic or inorganic bases, and including the metal complexes; have valuable microbicidal properties.