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A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.

The invention relates to quinazoline derivatives of formula (I) wherein m is an integer from 1 to 2; R.sup.1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkylthio, or --NR.sup.5 R.sup.6 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents hydrogen or C.sub.1-3 alkyl); R.sup.2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R.sup.3 represents hydroxy, halogeno, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X.sup.1 represents --O--, --CH.sub.2 --, --S--, --SO--, --SO.sub.2 --, --NR.sup.7 CO--, --CONR.sup.8 --, --SO.sub.2 NR.sup.9 --, --NR.sup.10 SO.sub.2 -- or --NR.sup.11 -- (wherein R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 each independently represents hydrogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl); R.sup.4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compostions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGP, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis. ##STR1##

The invention concerns the use of a compound of formula (I), in which Z, X, T, A, R.sup.1, R.sup.2, p and q have any of the meanings defined herein, and their pharmaceutically acceptable salts or in vivo hydrolysable esters, in the treatment of a disease or condition mediated by monocyte chemoattractant protein-1 (MCP-1). Certain of the components of formula (I) are novel and are provided, together with pharmaceutical compositions thereof, as further features of the invention.

A polymeric material comprising at least first and second polymer parts, which first part has a number average molecular weight higher than that of the second part and which first and second polymer parts each comprise a respective polymer part derived from at least one ethylenically unsaturated monomer, is prepared by a process which comprises the steps of (1) preparing, by aqueous suspension polymerisation the first, higher molecular weight polymer part in the presence of a free radical initiator, but in the absence of a chain transfer agent to form a suspension of the first, higher molecular weight part and thereafter (2) preparing by aqueous suspension polymerisation the second, lower molecular weight part, which preparation step (2) is carried out in the presence of the suspension of the first, higher molecular weight part, a free radical initiator and a catalytic chain transfer agent (CCTA). Step (2) may be continued to provide, additionally, a third polymer of a molecular weight intermediate that of the first and second polymers. A polymeric material thus obtainable has a PDi of at least 5 and a skewed molecular weight distribution in which the first-third polymers are present in successively increasing amounts. The polymeric material is especially suitable for use as a binder in a toner composition.

A dispersant of general Formula I wherein T is hydrogen or a polymerisation terminating group; Z is an acidic or basic group or a moiety containing either an acidic or basic group; A and B are each, independently, oxyalkylene carbonyl groups derivable from .delta.-valerolactone, .epsilon.-caprolactone or alkyl substituted .epsilon.-caprolactone provided that both are not .epsilon.-caprolactone or .delta.-valerolactone; n and p are integers; and n+p is from 2 to 100; including salts thereof. Specific examples of dispersants are the reaction product of lauric acid, .delta.-caprolactone, 7-methyl-.epsilon.-caprolactone with PEI, the reaction product of lauric acid, .epsilon.-caprolactone, .delta.-valerolactone with PEI and the phosphate of the reaction product of dodecanol, .epsilon.-caprolactone and .delta.-valerolactone.

The invention relates to a transgenic or mutated plant having genomic material which alters the normal starch synthesis pathway within the plant. More specifically, the present invention relates to a plant having a genotype which creates new forms of starch in significant quantity. Particularly, the invention relates to grain having an embryo with a genotype heterozygous for two or more wild type genes (for example, Aa/Bb) and an endosperm having a genotype heterozygous for such genes (for example, AAa/BBb or AAa/bbB or aaA/BBb or aaA/bbB) and the starch produced therefrom.

The invention concerns ##STR1## compounds of formula (I), wherein each of G.sup.1, G.sup.2 and G.sup.3 is CH or N; m is 1 or 2; R.sup.1 includes hydrogen, halogeno and 1-C)alkyl; M.sup.1 is a group of formula: NR.sup.2 --L.sup.1 --T.sup.1 R.sup.3, in which R.sup.2 and R.sup.3 together form a (1-4C)alylene group, L.sup.1 includes (1-4C)alkylene, and T.sup.1 is CH or N; A may be a direct link; M.sup.2 is a group of the formula: (T.sup.2 R.sup.4).sub.r L.sup.2 --T.sup.3 R.sup.5 in which R is 0 or 1, each of T.sup.2 and T.sup.3 is CH or N, each of R.sup.4 and R.sup.5 is hydrogen or (1-4C)alkyl, or R.sup.4 and R.sup.5 together form a (1-4C)alkylene group, and L.sup.2 includes (1-4C)alkylene; M.sup.3 may be a direct link to X; X includes sulphonyl; and Q includes naphthyl and a heterocyclic moiety; or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use as antithrombotic or anticoagulant agents.

A promoter comprising the DNA sequence of an oil seed rape cysteine protease gene promoter of class 1, 2 or 6 is described. The promoter may be used in an expression system for at least the tissue or tissues of a germinating seedling or developing grain or plant (e.g. in the root, cotyledons, leaves and stem). In a preferred embodiment, the expression system comprises a disrupter gene fused to a promoter according to the present invention.

1. An ink comprising water, a water-dissipatable polymer and a dye, wherein the dye carries a group of the Formula (1): ##STR1## wherein: R.sup.1 is optionally substituted branched chain alkyl; and R.sup.2 is H, optionally substituted alkyl or optionally substituted aryl. The inks are useful in ink jet printers.

cDNAs encoding mammalian AMP protein kinases, corresponding polypeptides and recombinant proteins together with antibodies thereto. Their uses including the study of gene expression and the characteristics of other proteins.

A method of modifying ethylene biosynthesis in a plant comprises inserting into the genome of the said plant a DNA sequence such as SEQ-ID-NO-1 (encoding 1-aminocyclopropane-1-carboxylic acid synthase (ACS)) and/or sequence SEQ-ID-NO-2 (encoding an ethylene-forming enzyme (EFE)) which modifies the activity of at least one of ACS or EFE. The method may be used to modify fruit ripening characteristics, especially in bananas.

Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs are substrates for carboxypeptidase G2 (CPG2) and yield more active cytotoxic drugs than known products of CPG2 catalysed reactions.

A process for producing an image on a substrate comprising printing an ink onto the substrate, characterized in that the ink contains a reactive dye, the substrate is an acid paper and the printing is performed by an ink jet printer. Also claimed is an acid paper printed by means of the process.

Compounds of formula (I) ##STR1## in which all variables are defined in the description and their salts inhibit the enzyme oxido squalene cyclase and are useful in treating hypercholesterolemia and also as anti-fungal agents. Processes for their preparation are also described together with their use in medicine.

This invention relates to single nucleotide polymorphisms in the LTC.sub.4 synthase gene, EMBL accession no. U50136, particularly at one or more of positions 375, 815, 1003, 2169 and 2742. The invention also relates to methods and materials for analyzing allelic variation in the LTC.sub.4 synthase gene, and to the use of LTC.sub.4 synthase polymorphism in tie diagnosis and treatment of leukotriene mediated diseases such as asthma and allergic rhinitis.

A method for the coloration of a substrate comprising ink jet printing a first and second set of inks onto the substrate wherein: (a) the first set of inks consists of one or more inks each of which independently contains a colorant selected from yellow, magenta, cyan and optionally black; and (b) the second set of inks comprises one or more inks each of which independently contains a dye selected from: a yellow dye of Formula (1) or salt thereof, an orange dye of Formula (2) or salt thereof, a red dye of Formula (3) or salt thereof and a blue dye of Formula (4) or salt thereof, wherein Formulae (1) to (4) are as defined in the description. Also claimed is a set of inks, ink jet printer cartridges, an ink jet printer and substrates printed using the printing method.

Microcapsules of a microcapsule formed of a polyurea shell wall and an encapsulated ingredient or ingredients enclosed within the wall, the wall comprising at least one oligomeric acetal having the moiety ##STR1## in which R is (a) a moiety containing a chain of from 5 to about 40 optionally substituted carbon atoms, (b) a moiety containing a chain of from 4 to about 40 carbon atoms and one or more internally linked oxygen or sulfur atoms or --NH-groups, or (c) an optionally substituted ethylene or propylene moiety Z is (a) an optionally substituted phenyl group, (b) an optionally substituted C.sub.1 -C.sub.20 alkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.3 -C.sub.8 cycloalkyl or C.sub.5 -C.sub.8 cycloalkenyl group, or (c) benzoyl, and n is 1 if R is (a) or (b), or is 2-20 if R is (c). The microcapsules are acid-sensitive and the capsule walls are relatively readily degraded or disintegrated by contacting the microcapsules with an acidic substance, preferably an organic or inorganic acid whereby the encapsulated ingredient or ingredients are released into the surrounding environment. The invention is particularly suitable for encapsulation of biologically active substances and agrochemicals, and most preferably pesticides for foliar treatment.

Antifungal proteins which are analogues of the Rs-AFP2 protein and contain particular mutations in their amino acid sequence. The mutated proteins possess enhanced salt-tolerant antifungal activity. The proteins are useful for combating fungal diseases in agricultural, pharmaceutical or preservative applications.

The invention relates to an insect steroid receptor protein which is capable of acting as a gene switch which is responsive to a chemical inducer enabling external control of the gene.

##STR1## This invention concerns heterocyclic derivatives of formula (I) which are useful in inhibiting oxido-squalene cyclase, processes for their preparation and pharmaceutical compositions containing them. The present invention is also concerned with heterocyclic derivatives capable of inhibiting cholesterol biosynthesis and hence the lowering cholesterol levels in blood plasma. The present invention also relates to methods of using such heterocyclic derivatives in diseases and medical conditions such as hypercholesterolemia and atherosclerosis.

Compounds of formula I ##STR1## wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

DNA sequence of an acetyl Coenzyme A carboxylase from plants are inserted into the genome of plants in sense or antisense orientation in order to inhibit expression of the gene product of the endogenous ACCase gene, resulting in reduced conversion of the enzyme's substrate, acetyl Coenzyme A, to fatty acid synthesis, leaving the substrate available for diversion into other biosynthesis pathways. One such diversion may be accomplished by providing the plant genome with genes specifying the synthesis of polyhydroxyalkanoate polymers.

The invention relates to heterocyclic derivatives, or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and more accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect, formula (I). ##STR1##

A compound of formula (I), ##STR1## or a pharmaceutically-acceptable salt thereof, wherein A is an optionally substituted 5- or 6-membered monocyclic aromatic ring containing 1, 2 or 3 ring heteroatoms; B is optionally substituted phenylene or a 6-membered heterocyclic ring containing 1, 2 or 3 nitrogen heteroatoms; R and R.sub.1 are hydrogen or (1-4C)alkyl; n is 1 or 2; R.sub.2 and R.sub.3 are hydrogen, (1-6C)alkyl, (4-7C)cycloalkyl, or (2-6C)alkenyl, or R.sub.2 and R.sub.3 may form along with the nitrogen to which they are attached a 5-, 6- or 7-membered heterocyclic ring, wherein each R.sub.2 or R.sub.3 group or any heterocyclic ring formed from R.sub.2 and R.sub.3 may be optionally substituted with various substituent groups, and wherein Q may be optionally substituted by various substituent groups, which posseses antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention relates to processes for the preparation of the compounds represented by formula (I), to pharmaceutical compositions containing them, and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

An improved T7 based promoter-driven protein expression system comprising an operator sequence downstream of the T7 promoter sequence, and having a further operator sequence upstream of the T7 promoter sequence.

This invention relates to derivatives of acrylic acid useful as fungicides, to processes for preparing them, to fungicidal compositions containing them, and to methods of combating fungi, especially fungal infections in plants, using them.

The present invention concerns the novel alkyl substituted heterocycles of formula I, set out below, wherein Q, Q.sup.1, Q.sup.2 and R have the values defined herein, which antagonize the pharmacological actions of one of the endogenous neuropeptide tachykinins at the neurokinin 2 (NK.sup.2) receptor making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the alkyl substituted heterocycles for use in such treatment, methods for their use, and processes and novel intermediates for their manufacture. ##STR1##

Compounds of formula I ##STR1## wherein J, B, L, X, m and M have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

The present invention provides a compound of the formula (I) ##STR1## wherein: R.sup.1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R.sup.2 is hydrogen or C.sub.1-4 alkyl; R.sup.3 and R.sup.4 are ortho with respect to one another wherein R.sup.3 and R.sup.4 are independently hydroxy or in vivo hydrolyzable esters thereof; the benzene ring being optionally further substituted; or a pharmaceutically acceptable salt or in vivo hydrolyzable ester thereof.

The present invention concerns novel carboxamide derivatives of formula I, set out hereinbelow which antagonize the pharmacological actions of one of the endogenous neuropeptide tachykinins at the neurokinin 2 (NK2) receptor, making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the novel carboxamide derivatives for use in such treatment, methods for their use, and processes and intermediates for the manufacture of the novel carboxamide derivatives. ##STR1##

The present invention concerns novel carboxamide derivatives of formula I, set out hereinbelow which antagonize the pharmacological actions of one of the endogenous neuropeptide tachykinins at the neurokinin 2 (NK2) receptor, making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the novel carboxamide derivatives for use in such treatment, methods for their use, and processes and intermediates for the manufacture of the novel carboxamide derivatives. ##STR1##

Compounds of formula I ##STR1## wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

The present invention concerns novel carboxamide derivatives of formula I, ##STR1## wherein R.sup.1, R.sup.2, J, m, and M have any of the values defined in the specification, which antagonize the pharmacological actions of one of the endogenous neuropeptide tachykinins at the neurokinin 2 (NK2) receptor, making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the novel carboxamide derivatives for use in such treatment, methods for their use, and processes and intermediates for the manufacture of the novel carboxamide derivatives.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Compounds of formula I ##STR1## wherein Q.sup.1, m and M have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

A method of administering to the eye a liquid ophthalmic formulation, comprising an ophthalmologically acceptable liquid and optionally containing an ophthalmologically-active substance, characterized in that the formulation has a viscosity in the range 10.sup.-3 to 1.0 Pa.s and a resistivity lower than 10.sup.4 ohm.cm, and that a jet of the formulation is ejected towards the eye, from a spray nozzle situated adjacent to a piezoelectric or electromagnetic transducer, to form a stream of uniformly-sized, equally spaced, uncharged droplets, the stream of uncharged droplets is subsequently directed past a charging electrode to induce an electric charge on each droplet in the stream, and the charged droplets discharge their electric charge by earthing on contact with the eye; and spraying apparatus suitable for use in that method.

The invention concerns pharmaceuticaly useful compounds of the formula I, in which Q, A.sup.1, A.sup.2, A.sup.3, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have any of the meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutically compositions containing them. The novel compounds possess endothelin receptor antagonist activity and are useful in the treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.

Compounds of formula I ##STR1## wherein J, B, L, X, m and M have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of SP and NKA are useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Pharmaceutical compositions containing 2,6-diisopropylphenol (propofol) are described for use as anaesthetics. A method for their preparation is described, as their use in producing anaesthesia including induction and maintenance of general anaesthesia and sedation.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

The invention relates to aminotetralin derivatives of the formula I: ##STR1## wherein: R.sup.1 is methyl or ethyl; R.sup.2 is hydrogen, halogen, lower-alkoxy or thiolower-alkyl; R.sup.3 is hydrogen, halogen, lower-alkoxy or lower-alkyl; and the chiral center * is in the (S)(-) form; or a pharmaceutically acceptable acid-addition salt thereof, with the proviso that when R.sup.2 and R.sup.3 are both hydrogen, R.sup.1 must be methyl; to pharmaceutical compositions containing them and to methods for the treatment or prevention of movement disorders utilizing them.

The present invention relates generally to a method of characterizing a sample of genomic DNA and to nucleotide sequences employed in the method as well as kits comprising these. In particular the invention involves the use of primers which selectively prime specific type(s) of internal repeat unit in a tandemly repeated region. The method of the invention is particularly useful in forensic or paternity studies and provides individual sample codes suitable for computerized storage on, and retrieval from, a database.

Method of preparing an optically active compound of formula, wherein R and R.sup.1 are independently alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, cycloalkyl, aryl, aralkyl, a heterocyclic group or a C.sub.1 -C.sub.4 alkyl-heterocycle, each being optionally substituted, procided that R and R.sup.1 are not identical and * is an optically active chiral center, from the corresponding racemic ester or diol by treating with a hydrolase enzyme. In particular, racemic 2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-1,2 diol, an intermediate in fluconazole synthesis, is resolved using porcine pancreatic lipase or lipase from Chromobacterium viscosum.

Plants with an altered starch synthesizing ability are produced by incorporating into the genome of the plant at least one donor gene encoding a starch primer. The starch primer is an enzyme capable of initiating starch synthesis, such as an amylogenin and/or glycogenin. DNA constructs encoding a starch primer are provided, particularly constructs encoding amylogenin from maize.

Compounds of formula I ##STR1## wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

The invention concerns pharmaceutically useful N-heterocyclyl sulphonamide derivatives, their pharmaceutically acceptable salts, processes for their manufacture, their use for antagonising one or more actions of endothelin in a human or other warm-blooded animal, their use in methods of treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role.

The invention concerns pharmaceutically useful compounds of the formula I, in which A.sup.1, A.sup.2, A.sup.3, A.sup.4, B.sup.1, m, Ar, W, X, Y, Z and R.sup.1 have any of the meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel compounds possess endothelin receptor antagonist activity and are useful, for example, in the treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, Q.sup.4 and Q.sup.5 have any of the meanings given in the specification, their N-oxides, and their pharmacuetically acceptable salts are nonpeptide antagonists NKA, useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Method of preparing an optically active compound of formula, wherein R and R.sup.1 are independently alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, cycloalkyl, aryl, aralkyl, a heterocyclic group or a C.sub.1 -C.sub.4 alkyl-heterocycle, each being optionally substituted, procided that R and R.sup.1 are not identical and * is an optically active chiral center, from the corresponding racemic ester or diol by treating with a hydrolase enzyme.

Filamentous microorganisms of improved properties, for example growth rate, may be obtained by culturing a sample of desired morphology until a substantial proportion of the culture diverges from that morphology, selecting an organism from the culture at that stage which exhibits the desired morphology and repeating the process with the selected microorganism. Furthermore, an isolated Fusarium graminearum having all of the characteristics of IMI 366464 and also possessing a greater morphological stability and growth rate than Fusarium graminearium strain IMI 145,425 is disclosed.

Biocidal proteins isolated from Mirabilis have been characterized. The proteins show a wide range of antifungal activity and are active against gram-positive bacteria. DNA encoding the proteins has been isolated and incorporated into vectors. Plants transformed with this DNA have been produced. The proteins find commercial application as antifungal or antibacterial agents; transformed plants will show increased disease-resistance.

A compound of formula (I), or a salt thereof, wherein n is 0, 1 or 2; and R is a group of formula (V) or (VII) ##STR1## wherein: at least one of R.sup.2, R.sup.3, R.sup.4 or R.sup.5 is a S(O)nCH.sub.2 CH.sub.2 CH.dbd.CF.sub.2 group; and the remainder of R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, alkoxy, alkenyloxy, alkynyloxy, hydroxyalkyl, alkoxyalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted arylalkoxy, optionally substituted aryloxyalkyl, optionally substituted heteroaryloxy, optionally substituted heteroarylalkoxy, optionally substituted heteroaryloxyalkyl, haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy, haloalkenyloxy, haloalkynyloxy, halogen, hydroxy, cyano, nitro, --NR.sup.7 R.sup.8, --NR.sup.7 COR.sup.8, --NR.sup.7 CSR.sup.8, --NR.sup.7 SO.sub.2 R.sup.8, --NR.sup.7 SO.sub.2 R.sup.8, --N(SO.sub.2 R.sup.7)(SO.sub.2 R.sup.8), --COR.sup.7, --CONR.sup.7 R.sup.8, -alkylCONR.sup.7 R.sup.8, --CR.sup.7 NR.sup.8, --COR.sup.7, --OCOR.sup.7, --SR.sup.7, --SOR.sup.7, --SO.sub.2 R.sup.7, -alkylSR.sup.7, -alkylSOR.sup.7, -alkylSO.sub.2 R.sup.7, --OSO.sub.2 R.sup.7, --SO.sub.2 NR.sup.7 R.sup.8, --CSNR.sup.7 R.sup.8, --CSNR.sup.7 R.sup.8, --SiR.sup.7 R.sup.8 R.sup.9, --OCH.sub.2 CO.sub.2 R.sup.7, --OCH.sub.2 CH.sub.2 SO.sub.2 R.sup.7, --CONR.sup.7 SO.sub.2 R.sup.8, -alkylCONR.sup.7 SO.sub.2 R.sup.8, --NHCONR.sup.7 R.sup.8, --NHCSNR.sup.7 R.sup.8 ; and R.sup.7, R.sup.8 and R.sup.9 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, alkynyl, optionally substituted aryl or optionally substituted arylalkyl, haloalkyl, haloalkenyl, haloalkynyl, halogen, or hydroxy; and agricultural compositions, and processes for preparing agricultural compositions made thereby.

Plants may be regenerated from stomatal cells or protoplasts of such cells. Prior to regeneration the cells or protoplasts may be genetically transformed by the introduction of hereditary material most preferably by a DNA construct which is free of genes which specify resistance to antibiotics. The regeneration step may include callus formation on a hormone-free medium. The method is particularly suitable for sugar beet.

A two component system for therapeutic treatment of a host, having a first component comprising a targeting moiety capable of binding with a tumour associated antigen, linked to a mutated enzyme capable of converting a prodrug into an antineoplastic drug, and a second component comprising a prodrug convertible under the influence of the mutated enzyme to the antineoplastic drug. The mutated enzyme is a mutated form of a natural host enzyme which recognizes its natural substrate by an ion pair interaction with the substrate, wherein the mutated enzyme and prodrug have structures such that the polarity of the mutated enzyme/prodrug ion pair interaction is reversed relative to the natural host enzyme/natural substrate ion pair interaction. The first component is substantially non-immunogenic in the host and the prodrug second component is not significantly convertible into antineoplastic drug in the host by natural unmutated host enzyme.

Biocidal proteins capable of isolation from seeds have been characterized. The proteins have an amino acid sequence containing the common cysteine/glycine domain of Chitin-binding Plant Proteins but show substantially better activity against pathogenic fungi, a higher ratio of basic amino acids to acidic amino acids, and/or antifungal activity which results in increased hyphal branching. Antimicrobial proteins isolated from Amaranthus, Capsicum, Briza and related species are provided. The proteins show a wide range of antifungal activity and are active against Gram-positive bacteria. DNA encoding the proteins may be isolated and incorporated into vectors. Plants may be transformed with this DNA. The proteins find agricultural or pharmaceutical application as antifungal or antibacterial agents. Transgenic plants expressing the protein will show increased disease resistance.

A method for making a mold including the steps of (a) forming a layer of a photocurable composition containing a U.V. transparent filler; (b) irradiating the layer formed in step (a) with light in a predetermined pattern thereby forming a solid cross-sectional layer of the desired mold; and (c) repeating steps (a) and (b) on the previously formed solid cross-sectional layer until the mold is formed. The filler is preferably phyllosilicate clay mineral and the mold has heat and pressure shock resistant properties making it particularly useful for injection molding.

A compound of formula (III) ##STR1## is produced by selectively reducing a compound of formula (II) ##STR2## using a reductase possessing the properties of one produced by Beauveria, Candida, Kluyveromyces, Torulaspora or Pichia. or A compound of formula ##STR3## is produced by selectively reducing a compound of formula II using a reductase possessing the properties of one produced by Candida pelliculosa, Neurospora crassa, Pichia trehalophila or preferably Hansenula anomola.

The use of a 2-(C.sub.3-5 -alkyl)-BIT or 2-aralkyl-BIT such as 2-phenylethyl-BIT as a fungicide for plastics materials. 2-n-Butyl-BIT is preferred.

A promoter derived from an SHH gene, especially the SHH gene of Arabidopsis thaliana which is capable of directing expression on a variety of operator genes in both monocotyledonous and dicotyledonous plants. The promoter of the invention may be used for directing expression of pathogen resistance genes to disease or wound sites.

Novel strains of the insecticidal microorganism Bacillus thurinaiensis are described. These contain novel genes, and in particular a gene coding for a novel insecticidal endotoxin, 81 kilodaltons in length, toxic to both Lepidoptera and Coleoptera. The novel strains and the genes they contain may be used to combat insect attack against plants.

The chemically-inducible 27 kD subunit of the enzyme glutathione-S-transferase, isoform II (GST-II-27) and sequences encoding it are provided. In particular, a genomic DNA sequence encoding the gene promoter for the GST-II-27 subunit is provided. Then linked to an exogenous gene and introduced into a plant by transformation, and GST-II-27 promoter provides a means for the external regulation of expression of that exogenous gene. Transformation with DNA encoding glutathione-S-transferase polypeptides produces herbicide resistance transgenic plants.

Compounds and ink compositions. An ink composition comprising a compound of Formula (1) and salts thereof: ##STR1## wherein Ch represents an arrangement of atoms which causes the compound to absorb electromagnetic radiation; R.sup.a and R.sup.b each independently is a spacer group; Y is an interactive functional group; w and x each independently is 0 or an integer equal to or greater than 1; and m and n each independently is an integer equal to or greater than 1, provided that w and x are not both equal to zero and when one of w or x is 0 at least one of m and n is equal to or greater than 2. For use in ink jet printing and electrophotography.

A herbicidal compound of formula (I): ##STR1## or N-oxide or quaternised derivative thereof; Ar is an optionally substituted aryl or heterocyclic ring system; W is O or NR.sup.1 where R.sup.1 is H or lower alkyl; A, B, D are independently selected from N, NR.sup.2, N--E, CR.sup.6, C--E or C(R.sup.6)E; wherein E is: ##STR2## provided 2 of A, B and D are N, NR.sup.2 or N--E; one of A, B and D is CR.sup.6, C--E or C(R.sup.6) E and at least one of A, B or D carries a group E; where R.sup.2 is H, OR.sup.7, CN, COOR.sup.8, alkyl or haloalkyl; R.sup.3 and R.sup.4 are independently selected from H, optionally substituted alkyl, alkenyl or alkynyl, halogen, NR.sup.9 R.sup.10, or R.sup.3 and R.sup.4 together with the carbon to which they are attached form an optically substituted alkenyl or cycloalkyl group; X is (CH.sub.2).sub.n, CH.dbd.CH, CH(OR.sup.16)CH.sub.2 or COCH.sub.2 where n is O, 1 or 2; R.sup.5 is CO.sub.2 R.sup.11, CN, COR.sup.11, CH(OH)R.sup.11, CH(OR.sup.11)R.sup.12, CSNH.sub.2, COSR.sup.11, CSOR.sup.11, CONHSO.sub.2 R.sup.11, CONR.sup.13 R.sup.14, CONHNR.sup.13 R.sup.14 R.sup.15 Y.sup.-, CO.sub.2,.sup.- M.sup.+ or COON.dbd.CR.sup.13 R.sup.14 ; R.sup.6 is H, halogen, OR.sup.7, CN, COOR.sup.8, alkyl or haloalkyl; and R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are specified organic groups.

Fungicidal compounds of the formula (I): ##STR1## and stereoisomers thereof, wherein R.sup.1 is optionally substituted aryl or optionally substituted heteroaryl; Y is oxygen, sulphur or NR.sup.4 ; R.sup.2, R.sup.3 and R.sup.4, which may be the same or different, are hydrogen, C.sub.1-4 alkyl or C.sub.2-4 alkenyl; X is halogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.1-4 alkoxy, nitro or cyano; and n is 0 or an integer of 1 to 4; provided that when Y is oxygen, n is 0 and R.sup.1 is unsubstituted phenyl at least one of R.sup.2 and R.sup.3 is other than hydrogen or methyl.

The invention provides compounds of formula (I) having nematicidal, insecticidal, acaricidal and fungicidal properties, compositions comprising them and processes and intermediates for their preparation: ##STR1## wherein: X is oxygen or sulphur; n is 0, 1 or 2; R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as described in the specification.

A method for killing or controlling weeds in a soya crop, which method comprises applying to the crop or to the location thereof a compound of formula (I): ##STR1## in an amount sufficient to kill the weeds but insufficient to kill the crop.

A stereoselective method for making compounds of Formula VIII ##STR1## wherein A and * are as defined in the specification. Enzymic processes and intermediates useful for preparing compound of Formula VIII are disclosed.

Compounds of formula I ##STR1## wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

A process for preparing agrochemical intermediates of formula (I), wherein W is (CH.sub.3 O).sub.2 CH.CHCO.sub.2 CH.sub.3 or CH.sub.3 O.CH.dbd.CCO.sub.2 CH.sub.3 ; Z.sup.1 is a halogen atom; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently hydrogen, halogen, C.sub.1-4 alky, C alkoxy, acetoxy or acyl; the process comprising the steps of: (a) reacting a compound of formula (II), wherein X, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above, with a compound of formula ROCH.sub.3, wherein R is a metal; and, (b) reacting the product of (a) with a compound of formula (III), wherein Z.sup.1 and Z.sup.2 are halogen atoms. A process for the preparation of compounds of formula (II) and compounds of formula (II) themselves. A process for obtaining, in substantially pure form, a compound of formula (11) and compounds of formula (II) themselves. A process for obtaining, in substantially pure form, a compound of formula (11) wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are all hydrogen.

An agrochemical composition packaged in a water soluble or water dispersible sachet is taught. The agrochemical composition is comprised of water-soluble, agrochemically active agent, water and an agent to minimize water loss through the walls of the sachet, wherein the is an ester of an alkyl, alkenyl, aryl, or arylalkyl acid; an ester or a naturally occurring oil; or a mineral or a synthetic oil; provided that the agent is not dibutylphtalate.

A method of characterizing a test sample of genomic DNA which method comprises contacting the test sample with type specific primer to prime selectively, within a telomere repeat array, internal repeat units of that type, and extending the type specific primers in the presence of appropriate nucleoside triphosphates and an agent for polymerization thereof to produce a set of amplification products extending from the internal repeat units of that type to at least the end of the telomere repeat array.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, Q.sup.4 and Q.sup.5 have any of the meanings given in the specification, their N-oxides, and their pharmacuetically acceptable salts are nonpeptide antagonists NKA, useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

##STR1## The present invention relates to inhibitors of ras farnesylation of Formula (I), wherein T is of Formula (1) or (2) or (3); A is aryl or heteroaryl; B is aryl or heteroaryl; X and Y represent hydrogen, or both X and Y can represent a single bond (so as to form a double bond); R.sup.1 represents a group of Formula (II) or (III), the group of Formula (II) or Formula (III) (having L or D configuration at the chiral alpha carbon in the corresponding free amino acid); R.sup.2 represents hydrogen, aryl or heteroaryl; Z represents a direct bond, methylene, ethylene, vinylene, oxy, --CH.sub.2 --O-- or --O--CH.sub.2 --; and R.sup.3 --R.sup.4, p and r are as defined in the specification or a pharmaceutically-acceptable salt, prodrug or solvate thereof. Processes for their preparation, their use as therapeutic agents and pharmaceutical compositions containing them. A particular use is in cancer therapy

A method for the prophylaxis or treatment of conditions for which 5-HT.sub.1 -like agonists are indicated comprising the administration of therapeutically-effective amount of compounds of formula (I) ##STR1## wherein A, W, Z and n are as defined in the specification.

The present invention relates to certain novel substituted derivatives which are 1-pyrimidinylacetamide derivatives of formula I, ##STR1## which are inhibitors of human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated. The invention also includes intermediates useful in the synthesis of these substituted derivatives, processes for preparing the substituted derivatives, pharmaceutical compositions containing such substituted derivatives and methods for their use.

The present invention relates to particular forms of a novel 1-substituted-N-[2-methyl-1-(trifluoroacetyl)propyl]pyrrolidine-2-carboxam ide which are inhibitors of human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated. The invention also includes pharmaceutical compositions containing such forms, processes for preparing the forms and intermediates useful in the synthesis of the forms.

A compound of formula (I): ##STR1## where E is oxygen or sulphur; A is CR.sup.3 or N where R.sup.3 is hydrogen or hydrocarbyl; D completes a 5 or 6-membered non-aromatic heterocyclic ring which optionally contains additional heteroatoms selected from oxygen, nitrogen or sulphur and which is optionally substituted by an optionally substituted lower hydrocarbyl group, or an optionally substituted heteroaryl group; R.sup.1 and R.sup.2 are each independently hydrogen; optionally substituted lower hydrocarbyl, or optionally substituted heteroaryl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached, form a heterocyclic ring; Z represents halogen optionally substituted lower hydrocarbyl, optionally substituted lower hydocarbyloxy, optionally substituted lower hydrocarbylthio, hydrocarbylsulphinyl or hydrocarbylsulphonyl, cyano, nitro, CHO, NHOH, ONR.sup.7' R.sup.7", SF.sub.5 ; CO (optionally substituted lower hydrocarbyl), acylamino, COOR.sup.7, SO.sub.2 NR.sup.8 R.sup.9, CONR.sup.10 R.sup.11, OR.sup.12 or NR.sup.13 R.sup.14 where R.sup.7, R.sup.7', R.sup.7", R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or lower hydrocarbyl; R.sup.12 is hydrogen; SO.sub.2 lower hydrocarbyl or COR.sup.15 ; R.sup.13 and R.sup.14 are independently lower hydrocarbyl, lower hydrocarbyloxy or a group R.sup.12 ; R.sup.15 is OR.sup.16, NR.sup.17 R.sup.18, hydrogen or lower hydrocarbyl; R.sup.16 is lower hydrocarbyl; R.sup.17 and R.sup.18 are independently hydrogen or lower hydrocarbyl; provided that when there are two or more substituents Z, they may be the same or different; and m is 0 or an integer from 1 to 5.

A glyphosate composition comprises (I) N-phosphonomethylglycine or an agriculturally acceptable salt thereof, (ii) an alkyl polyglycoside surfactant, (iii) an ethoxylated alcohol, for example an ethoxylated alcohol obtained by ethoxylation of a linear or branched chain aliphatic mono alcohol having a chain length of from 8 to 20 carbon atoms and a mean degree of ethoxylation of from 2 to 50 moles of ethylene oxide per mole of alcohol, and optionally (iv) an additional surfactant, and optionally (v) a humectant.

The present invention relates to pyrrolidine derivatives, and more particularly to the compound (S)-1-[(S)-2-(4-methoxybenzamido)-3-methylbutyryl]-N-[(S)-2-methyl-1-(trif luoroacetyl)propyl]pyrrolidine-2-carboxamide, shown by formula I, and solvates thereof. The present invention also provides pharmaceutical compositions, intermediates and methods of preparation of the compound. The compound of formula I is an inhibitor of human neutrophil elastase and is useful in the treatment of diseases in which the enzyme is implicated, such as, for example, emphysema and acute respiratory distress syndrome (ARDS).

A compound having the formula R--S(O).sub.n CH.sub.2 CH.sub.2 CH.dbd.CF.sub.2, or a salt thereof, wherein R is a phenyl group or a heterocyclic group selected from furyl, thienyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,3,4-triazinyl and 1,3,5-triazinyl groups, said phenyl or heterocyclic group being optionally substituted by optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, cycloalkyl, alkylcycloalkyl, alkoxy, alkenyloxy, alkynyloxy, hydroxyalkyl, alkoxyalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted arylalkoxy, optionally substituted aryloxyalkyl, optionally substituted heteroaryloxy, optionally substituted heteroarylalkoxy, optionally substituted heteroaryloxyalkyl, haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy, haloalkenyloxy, haloalkynyloxy, halogen, hydroxy, cyano, nitro, --NR7R8, --NR7COR8, --NR7CSR8, --NR7SO2R8, --N(SO2R7)(SO2R8), --COR7, --CONR7R8, -alkylCONR7R8, --CR7NR8, --COOR7, --OCOR7, --SR7, --SOR7, --SO2R7, -alkylSR7, -alkylSOR7, -alkylSO2R7, --OSO2R7, --SO2NR7R8, --CSNR7R8, --SiR7R8R9, --OCH2CO2R7, --OCH2CH2CO2R7, --CONR7SO2R8, -alkylCONR7SO2R8, --NHCONR7R8, --NHCSNR7R8, or an adjacent pair of R1, R2, R3, R4, R5 and R6 when taken together form a fused 5- or 6-membered carbocyclic or heterocyclic ring; and R7, R8 and R9 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, alkynyl, optionally substituted aryl or optionally substituted arylalkyl, haloalkyl, haloalkenyl, haloalkynyl, halogen, or hydroxy.

Fungicidal compounds having the formula (I): ##STR1## in which any two of K, L and M are nitrogen and the other is CA wherein A is H, halogen, C.sub.1-4 alkyl, cyano, nitro or trifluoromethyl; X is a linking group other than oxygen; T is oxygen or sulphur; and Z is an optionally substituted carbocyclic or heterocyclic ring.

A compound of formula (I), wherein A is C.sub.1-6 alkyl, --O--C.sub.1-6 alkyl, --O--phenyl or phenyl, optionally substituted by C.sub.1-3 alkyl or halogen; n is an integer of from 0 to 3; W is a group of formula (i), (ii) or (iii) where R is hydrogen or C.sub.1-4 alkyl, x is --O--, --S--, --NH--, or --CH.sub.2 --, Y is oxygen or sulphur and the chiral centre * in formula (i) or (ii) is in its (S) or (R) form or is a mixture thereof in any proportions; and Z is a group of formula (iv) --HC.sub.2 CH.sub.2 NR.sup.1 R.sup.2 (v) or (vi) where R.sup.1 and R.sup.2 are independently selected from hydrogen and C.sub.1-4 alkyl and R.sup.3 is hydrogen or C.sub.1-4 alkyl; and salts, solvates and physiologically functional derivatives thereof. ##STR1##

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Compounds of formula I ##STR1## wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of SP and NKA are useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

New and useful herbicidal compositions comprising N-phosphonomethylglycineor an agriculturally acceptable salt thereof, an ethoxylated alkyl glycoside surfactant, and an ethoxylated alcohol are provided.

The present invention relates to pyrrolidine derivative compounds, and more particularly to the compound (S)-1-[(S)-2-(4-methoxybenzamido)-3-methylbutyryl]-N-[(S)-2-methyl-1-(trif luoroacetyl)propyl]pyrrolidine-2-carboxamide, shown by the formula I, a pharmaceutical composition comprising this compound in a crystalline form and a process for preparing the pharmaceutical composition. The compound of formula I is an inhibitor of human neutrophil elastase and is useful in the treatment of diseases in which the enzyme is implicated, such as, for example, emphysema and acute respiratory distress syndrome (ARDS).

The present invention relates to particular forms of a novel 1-substituted-N-[2-methyl-1-(trifluoroacetyl)propyl]pyrrolidine-2-carboxam ide which are inhibitors of human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated. The invention also includes pharmaceutical compositions containing such forms, processes for preparing the forms and intermediates useful in the synthesis of the forms.

The present invention relates to particular forms of a novel 1-substituted-N-[2-methyl-1-(trifluoroacetyl)propyl]pyrrolidine-2-carboxam ide which are inhibitors of human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated. The invention also includes pharmaceutical compositions containing such forms, processes for preparing the forms and intermediates useful in the synthesis of the forms.

The invention concerns pharmaceutically useful compounds of the formula I, in which A.sup.1, A.sup.2, A.sup.3, A.sup.4, B.sup.1, m, Ar, W, X, Y, Z and R.sup.1 have any of the meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel compounds possess endothelin receptor antagonist activity and are useful, for example, in the treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.

Pyrimidine sulphonamide compounds of the following formula, ##STR1## wherein Q is a naphthyl or biphenyl group either unsubstituted or substituted with A.sup.1, and where A.sup.1, R.sup.1 and R.sup.2 are a variety of alkyl, aryl and cyclic moieties, as described in the specification hereof, which compounds are useful for the treatment of diseases or medical conditions such as hypertension, pulmonary hypertension, cardiac or cerebral circulatory disease and renal disease.

A granule suitable for aqueous spray application after tank mix dispersion or dissolution comprises an active ingredient or auxiliary agent, an inert filler and a water-swellable material wherein the water-swellable material is incorporated into the granule in a substantially dry form. Preferred water-swellable materials are non-ionic or predominantly non-ionic and an especially preferred water-swellable material is Xantham gum. The granules provide reduced sludge residues in the spray tank and are particularly well suited for use when housed in a water-soluble bag.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists Substance P and NKA, useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, Q.sup.4 and Q.sup.5 have any of the meanings given in the specification, their N-oxides, and their pharmacuetically acceptable salts are nonpeptide antagonists NKA, useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

A compound of the general formula ##STR1## or a salt or complex thereof, in which X, Y and Z are all optionally substituted carbon atoms and R is hydrogen, optionally substituted hydrocarbyl or acyl or --COOR.sup.7 and R.sup.7 is hydrocarbyl has anti-microbial properties. Particular examples are compounds in which X is --CH.sub.2 -- or --C(CH.sub.3).sub.2 -- and Y and Z are both --CH.sub.2 -- or X is is --CH.sub.2 -- and Y and Z are carbon atoms of a benzene ring. The zinc complexes have useful properties.

Herbicidal compounds have the formula ##STR1## in which R.sub.1 is hydrogen, methyl, ethyl, phenyl, 2-methylphenyl, 3-trifluoromethylphenyl, benzyl, 2-methylbenzyl or vinyl; R.sub.2 is hydrogen, methyl, ethyl or chloro; R.sub.3 is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkyl, nitro, p-tolyloxy or p-chlorophenoxy; R.sub.4 is hydrogen or a methyl, methoxy, trifluoromethoxy or halo group at the 2, 4- or 5-position; m is --CH or N; and X is O or NOR.sub.5 in which R.sub.5 is methyl or ethyl; provided that: (a) when R.sub.1 is methyl, and (i) R.sub.3 is methyl, then R.sub.4 is 4-methyl, 4-methoxy or chloro; (ii) R.sub.3 is nitro, then R.sub.4 is methoxy; (b) when R.sub.1 is ethyl, R.sub.3 is methyl or methoxy; (c) when R.sub.2 is chloro, R.sub.3 and R.sub.4 are independently C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 haloalkoxy or C.sub.1 -C.sub.4 alkoxy; (d) when R.sub.2 is methyl or ethyl, R.sub.1 is hydrogen; (e) when R.sub.3 is hydrogen, R.sub.4 is 2-methyl, halo or methoxy; (f) if M is N, R.sub.3 is C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkyl or C.sub.1 -C.sub.4 haloalkoxy and R.sub.1 is not ethyl; and (g) if R.sub.1 is vinyl, M is N.

Biocidal proteins capable of isolation from seeds have been characterized. The proteins have an amino acid sequence containing the common cysteine/glycine domain of Chitin-binding Plant Proteins but show substantially better activity against pathogenic fungi, a higher ratio of basic amino acids to acidic amino acids, and/or antifungal activity which results in increased hyphal branching. Antimicrobial proteins isolated from Amaranthus, Capsicum, Briza and related species are provided. The proteins show a wide range of antifungal activity and are active against Gram-positive bacteria. DNA encoding the proteins may be isolated and incorporated into vectors. Plants may be transformed with this DNA. The proteins find agricultural or pharmaceutical application as antifungal or antibacterial agents. Transgenic plants expressing the protein will show increased disease resistance.

The present invention relates to certain novel heterocyclic amides which are 1-pyridylacetamide compounds of formula I, set out herein, which are inhibitors of human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated. The invention also includes intermediates useful in the synthesis of these heterocyclic amides, processes for preparing the heterocyclic amides, pharmaceutical compositions containing such heterocyclic amides and methods for their use.