摘要:
This invention relates to a novel farnesylated dibenzodiazepinone, named ECO-04601, its pharmaceutically acceptable salts and derivatives, and to methods for obtaining such compounds. One method of obtaining the ECO-04601 compound is by cultivation of a novel strain of Micromonospora sp., 046-ECO11; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates to Micromonospora sp. strain 046-ECO11, to the use of ECO-04601 and its pharmaceutically acceptable salts and derivatives as pharmaceuticals, in particular to their use as inhibitors of cancer cell growth, bacterial cell growth, mammalian lipoxygenase, and to pharmaceutical compositions comprising ECO-04601 or a pharmaceutically acceptable salt or derivative thereof. Finally, the invention relates to novel polynucleotide sequences and their encoded proteins, which are involved in the biosynthesis of ECO-04601.
摘要:
A method to produce novel polyketide structures by designing and introducing specified changes in the DNA governing the synthesis of the polyketide is disclosed. The biosynthesis of specific polyketide analogs is accomplished by genetic manipulation of a polyketide-producing microorganism by isolating a polyketide biosynthetic gene-containing DNA sequence, identifying enzymatic activities associated within the DNA sequence, introducing one or more specified changes into the DNA sequence which codes for one of the enzymatic activities which results in an altered DNA sequence, introducing the altered DNA sequence into the polyketide-producing microorganism to replace the original sequence, growing a culture of the altered microorganism under conditions suitable for the formation of the specific polyketide analog, and isolating the specific polyketide analog from the culture. The method is most useful when the segment of the chromosome modified is involved in an enzymatic activity associated with polyketide biosynthesis, particularly for manipulating polyketide synthase genes from Saccarharopolyspora or Streptomyces.
摘要:
Novel antifungal agents having the formula: ##STR1## wherein R is hydrogen or a radical of the formula ##STR2## and pharmaceutically acceptable prodrugs thereof, as well as (i) pharmaceutical compositions comprising such compounds, (ii) methods of treatment using such compounds, and (iv) methods and fungal cultures useful in making the same.
摘要:
Compounds having the formula ##STR1## wherein --OR.sup.1 comprises the C-13 side-chain of taxol and R.sup.3 comprises hydrogen, as well as a method for the preparation thereof.
摘要:
An improved method of producing 2-epi-fortimicin A directly from fortimicin A by protecting the amine functions of fortimicin A, converting the N-protected fortimicin A to an intermediate of the formula: ##STR1## wherein L is a leaving group and Z is an amine-protecting group, reacting the intermediate (I) with a loweralkyl metal halide in N,N-dimethylformamide to form N-protected-2-epi-fortimicin A, and then hydrogenating the N-protected-2-epi-fortimicin A to obtain 2-epi-fortimicin A.
摘要翻译:通过保护苦丁霉素A的胺官能团,将N-保护的fortimicin A转化为下式的中间体,其中L是离去基团,其中L是离去基团 并且Z是胺保护基团,使中间体(I)与N,N-二甲基甲酰胺中的低级烷基金属卤化物反应,形成N-保护的2-表 - 敌霉素A,然后将N-保护的2-表面 - 有益霉素A获得2-epi-fortimicin A.
摘要:
Described are novel derivatives of seldomycin factor 5 (XK-88-5) and particularly 3'-Epi-seldomycin factor 5, which exhibit improved activity against gram-positive and gram-negative bacteria resistant to aminoglycoside antibiotics, and a method of preparing them.
摘要:
The invention relates to biologically active dibenzodiazepinone analogs represented by Formula I, to methods of producing them, to pharmaceutical compositions comprising them and to methods of treating neoplastic conditions.
摘要:
This invention relates to novel biologically active polyene oxazoles, their pharmaceutically acceptable salts and derivatives, and to methods of obtaining them. One method for obtaining the compounds is by cultivation of Streptomyces sparsogenes NRRL 2940 or a mutant or variant thereof.
摘要:
A method for treating a fungal infection is disclosed. The method includes administering to a patient a pharmaceutical composition containing a compound of formula (IA): where each R is independently H, OH, Br, Cl, I, amino, thiol, nitro, C1-4 alkoxy, C1-4 alkenyloxy, C2-6 alkoxyalkyleneoxy, C1-4 alkylthio, C3-18 alkyl, or C3-18 alkenyl; or two adjacent R's, taken together, are a C2-18 bivalent moiety containing at least one oxgen atom, substituted or disubstituted with A or B or both, A being H, OH, Br, Cl, I, amino, or thiol, and B being H, C1-10 alkyl, C2-18 alkenyl, or C6-18 aryl; provided at least two Rs are not H; X is C4-10 alkyl, C4-20 alkenyl, or a C4-20 single, C6-20 bridged, or C6-20 fused ring moiety containing cycloalkyl, cycloalkenyl, aryl, heterocycle, or heteroaryl, where X is substituted with H, OH, Cl, Br, I, amino, cyano, nitro, alkyl, alkoxy, alkenyl, or alkenyloxy; provided that if X is a heteroaryl or heterocyclic moiety where two Rs are each OH and meta to each other, then the remaining R is H and ortho to each of the two hydroxyls, and Y and Z are each O and a ring atom of X is linked directly to the sp2 carbon atom adjacent to X, then substituted with H, OH, Cl, Br, I, amino, cyano, alkyl, alkoxy, alkenyl, or alkenyloxy; and each of Y and Z is independently selected from O, S, and NH; or a pharmaceutically acceptable salt or ester thereof.
摘要:
Novel antifungal and antitumor agents having the formula ##STR1## as well as pharmaceutically acceptable salts, esters, amides and pro-drugs thereof, wherein R is selected from the group consisting of ##STR2## Also disclosed are pharmaceutical compositions comprising such compounds, and methods of treatment and processes of manufacture relating thereto.