Abstract: The present invention relates to novel DNA sequences that encode for the branched-chain alpha-ketoacid dehydrogenase complex of an organism belonging to the genus Streptomyces and to novel polypeptides produced by the expression of such sequences. It also relates to novel methods of enhancing the production of natural avermectin and of producing novel avermectin through fermentation.

Abstract: An infection with Helicobacter may successfully be treated with a compound of the formula ##STR1## wherein R.sub.1 is hydrogen or methyl and R.sub.2 is hydrogen or L-alanine-L-alanyl, and the pharmaceutically acceptable acid additive salts thereof. These compounds are useful in the treatment of gastric and duodenal ulcers.

Abstract: This invention relates to methods of inhibiting sorbitol dehydrogenase, lowering fructose levels, and treating or preventing diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic microangiopathy or diabetic macroangiopathy in a mammal using pyrimidine derivatives of formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are defined as below, and to pharmaceutical compositions containing such derivatives. It also relates to certain novel substituted pyrimidines having the above formula. It also relates to mutual prodrugs of compounds of above formula (I) and aldose reductase inhibiting compounds, and to pharmaceutical compositions comprising a compound of above formula (I) and an aldose reductase inhibitor.

Abstract: The present invention provides novel methods of inhibiting reperfusion damage in ischemic myocardium comprising administering to a mammal in need of such treatment an effective amount of a compound of formula I ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different provided that, when R.sup.1 and R.sup.2 are the same, each is a methyl or ethyl group, and, when R.sup.1 and R.sup.2 are different, one of them is a methyl or ethyl group and the other is hydrogen or a benzyl group; or a pharmaceutically acceptable salt thereof.

Abstract: A compound of formula (I): ##STR1## wherein the broken lines represent independently optional bonds, R.sup.1 and R.sup.2 being absent when the C.sub.22 -C.sub.23 double bond is present.

Abstract: The present invention relates to novel substituted benzylamino nitrogen containing non-aromatic heterocycles and, specifically, to compounds of the formula ##STR1## wherein W, R.sup.1, R.sup.2, R.sup.3 and A are as defined in the specification, and to intermediates used in the synthesis of such compounds. The novel compounds of formula I are useful in the treatment of inflammatory and central nervous system disorders, as well as other disorders.

Abstract: Compounds of formula (I): ##STR1## wherein R.sup.1 is hydrogen or methyl, R.sup.2 is hydrogen or (E)-2-methyl 2-butenoyloxy, and R.sup.3 is hydrogen or hydroxy, with the proviso that when R.sup.3 is hydrogen, R.sup.1 and R.sup.2 are both hydrogen, and when R.sup.2 is (E)-2-methyl 2-butenoyloxy, R.sup.1 is methyl; the compound of formula (II): ##STR2## and the compound of formula (III): ##STR3## are obtainable by the fermentation of Streptomyces E225 NCIB 12310 or Streptomyces E225B NCIB 12509. The compounds have anthelmintic utility.

Abstract: The present invention provides novel methods of inhibiting myeloperoxidase activity comprising administering to a mammal in need of such treatment an effective amount of a compound of formula I ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different provided that, when R.sup.1 and R.sup.2 are the same, each is a methyl or ethyl group, and, when R.sup.1 and R.sup.2 are different, one of them is a methyl or ethyl group and the other is hydrogen or a benzyl group; or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides novel methods of inhibiting Alzheimer's Disease comprising administering to a human in need of treatment an effective amount of a compound of formula I ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different provided that, when R.sup.1 and R.sup.2 are the same, each is a methyl or ethyl group, and, when R.sup.1 and R.sup.2 are different, one of them is a methyl or ethyl group and the other is hydrogen or a benzyl group; or a pharmaceutically acceptable salt thereof.

Abstract: Optically pure intermediates of formula (1) wherein the substituent B is either cis or trans to the C.sub.9a -C.sub.1 bond and is selected from the group consisting of --CH.sub.2 OH, --CHO, --CH.sub.2 OSO.sub.2 R, --CH.sub.2 CN, --CH(OH)CH.sub.2 NO.sub.2, --CH.dbd.CH--NO.sub.2, (2) and (3), C is selected from the group consisting of --H, (4), (5), and a nitrogen protecting group which is removable by hydrogenation or acid treatment; and wherein R is (C.sub.1 -C.sub.8) alkyl, phenyl or alkyl substituted phenyl; X is N or CH; Y is O or S and Z is H or Cl; for the synthesis of octahydro-1H-pyrido(1,2-a)pyrazinyl ethyl carboxamide anxiolytic agents.

Abstract: Compounds of the formula ##STR1## wherein R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, C.sub.3 -C.sub.5 cycloalkyl or C.sub.1 -C.sub.3 perfluoroalkyl;R.sup.2 is H, C.sub.1 -C.sub.6 alkyl optionally substituted by OH, C.sub.1 -C.sub.3 alkoxy or C.sub.3 -C.sub.6 cycloalkyl, or C.sub.1 -C.sub.3 perfluoroalkyl;R.sup.3 is H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 alkynyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 perfluoroalkyl or (C.sub.3 -C.sub.6 cycloalkyl)C.sub.1 -C.sub.6 alkyl;and Y is chloro, bromo, or fluoro.The above compounds are intermediates useful in the synthesis of certain pyrazolopyrimidinones which inhibit cyclic guanosine 3', 5'-monophosphate phosphodiesterase.

Abstract: A method of treating tinnitus in a mammal in need of such treatment, in which the method comprises administering a therapeutically effective amount of a compound of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 -R.sup.6 are as defined herein.

Abstract: This invention relates to isoxazoline compounds which are selective inhibitors of phosphodiesterase type IV (PDE.sub.IV). The isoxazoline compounds are useful in inhibiting PDE.sub.IV and in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease, psoriasis, allergic rhinitis, dermatitis, shock, atopic dermatitis, rheumatoid arthritis and osteoarthritis. This invention also relates to pharmaceutical compositions useful therefor.

Abstract: A compound of formula (I) or a salt thereof, wherein R.sup.1 is hydrogen, methoxy or formamido; R.sup.2 is an acyl group, in particular that of an antibacterially active cephalosporin; CO.sub.2 R.sup.3 is a carboxy group or a carboxylate anion, or R.sup.3 is a readily removable carboxy protecting group or a pharmaceutically acceptable salt-forming group or in vivo hydrolysable ester group; R.sup.4 represents hydrogen or up to four substituents, which may be present on any of the carbon atoms in the ring system shown, selected from alkyl, alkenyl, alkynyl, alkoxy, hydroxy, halogen, amino, alkylamino, acylamino, dialkylamino, CO.sub.2 R, CONR.sub.2, SO.sub.2 NR.sub.2 where R is hydrogen or alkyl, aryl and heterocyclyl, which may be the same or different and wherein any R.sup.4 alkyl substituent is optionally substituted by one or more substituents selected from the list from which R.sup.4 is selected; Y is O, S, SO or SO.sub.

Abstract: Compounds of the formula ##STR1## wherein W, Ar.sup.1, Ar.sup.2 and Ar.sup.3 are defined as below; and the pharmaceutically acceptable salts of such compounds.These compounds are substance P antagonists and useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.

Abstract: Compounds of the formula ##STR1## where A represents a direct bond, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl; n is 0, 1, or 2; R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, C.sub.1 -C.sub.3 alkylaryl, C.sub.1 -C.sub.3 alkylheteroaryl, or --(CH.sub.2).sub.m R.sub.6 ; W, X, Y, and Z are each independently oxygen, sulfur, nitrogen or carbon, provided that at least one of W, X, Y or Z is nitrogen; R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, C.sub.1 -C.sub.3 alkylaryl, C.sub.1 -C.sub.3 alkylheteroaryl, halogen, cyano, trifluommethyl, nitro, --OR.sub.7, --NR.sub.7 R.sub.8, --(CH.sub.2).sub.s OR.sub.7, --SR.sub.7, --SO.sub.2 NR.sub.7 R.sub.8, --NR.sub.7 SO.sub.2 R.sub.8, --NR.sub.7 CO.sub.2 R.sub.8, --CONR.sub.7 R.sub.8, or --CO.sub.2 R.sub.7 ; one of R.sub.2 and R.sub.3, R.sub.3 and R.sub.4, or R.sub.4 and R.sub.

Abstract: The present invention relates to amide derivatives of formula (I) or (II) of 19-carboxy-19-deformyl 16-membered ring macrolide antibiotics rosaramicin, repromicin, tylosin, 5-O-mycaminosyltylonolide, 4-deoxy-O-mycaminosyltylonolide, desmycosin lactenocin, O-demethyllactenocin, cirramycin A.sub.1, and 23-deoxymycaminosyltylonolide, which are useful against bacterial and mycoplasmic pathogens in animals. Also claimed are a pharmaceutical composition of such derivatives and their use in treating bacterial and mycoplasmic infections in animals.

Abstract: The invention provides a process for preparing a compound of the formula: ##STR1## or a base salt thereof, wherein R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl optionally substituted by up to 3 substituents each independently selected from the group consisting of C.sub.1 -C.sub.6 alkoxy and C.sub.1 -C.sub.6 alkoxy(C.sub.1 -C.sub.6 alkoxy)-; and R.sup.3 is C.sub.1 -C.sub.6 alkyl or benzyl, said benzyl group being optionally ring-substituted by up to 2 nitro or C.sub.1 -C.sub.4 alkoxy substituents. comprising reacting a compound of the formula: ##STR2## wherein R.sup.1 is C.sub.1 -C.sub.4 alkyl, phenyl or benzyl or C.sub.1 -C.sub.4 alkoxy; and R.sup.2 and R.sup.3 are as previously defined for a compound of the formula (I), with hydrogen peroxide or a source of peroxide ions: said process being optionally followed by conversion of the compound of the formula (I) to a base salt thereof. The present invention also relates to novel compounds of the formula (II).

Abstract: This invention relates to compounds of formula I ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, X, m and n are defined as in the specification, their pharmaceutically acceptable salts and pharmaceutical compositions containing such compounds or their salts.