Showing papers by "Eli Lilly and Company published in 1979"
TL;DR: The formamide acetals as mentioned in this paper have been used in two main categories of reactions, namely alkylation and formylation, and are used in the synthesis of esters from acids, ethers and thioethers from phenols and aromatic and heterocyclic thiols.
233 citations
TL;DR: The loss in β-adrenergic receptor binding does not correlate in a temporal fashion with the reported decrease in norepinephrine-stimulated cyclic AMP accumulation in the cerebellum which occurs as early as 12 months of age.
169 citations
01 Jan 1979
TL;DR: Antibiotic-blocked mutants have been used in several recent biosynthetic studies and their utility in the synthesis of new antibiotics via interspecific matings is discussed, and gene-transfer in microorganisms is discussed.
Abstract: Publisher Summary The general characteristics and uses of antibiotic-blocked mutants and their application in mutasynthetic studies of aminocyclitol antibiotics have been reviewed recently. This chapter discusses their utility in the synthesis of new antibiotics via interspecific matings. Antibiotic-blocked mutants have been used in several recent biosynthetic studies. Two types of cephalosporin C (CPC)-blocked mutants of Cephalosporium acremonium were used in studying cell-free ring-expansion of penicillin N (pen N) to deacetoxycephalosporin C (DXPC). The chapter also discusses gene-transfer in microorganisms. Gene transfer in microorganisms can be brought about by manipulations, involving in one step, bringing cells of genotypically different strains together so that the cell contact is physically possible. The advantages of using both mutation and genetic recombination in industrial strain improvement programs and in genetic analyses required for more sophisticated genetic manipulations have been stressed by Hopwood and collaborators. Prior to 1977, the only technique available to effect genetic recombination in the industrially important genus Streptomyces was natural conjugation.
143 citations
TL;DR: There appears to be some correlation between activity in endogenous opioid systems and the ability of mice to withstand noxious stimuli.
107 citations
TL;DR: The behavioral and neuroendocrine effects of this new ergoline compound and its reduction of dopamine turnover in rat brain indicate that it is a potent dopamine receptor agonist in vivo.
102 citations
TL;DR: The results indicate that VIP can cause prolactin release by a direct action on anterior pituitary lactotrophes and addition of bacitracin or bovine serum albumin to the culture medium must prevent VIP from binding to glass.
84 citations
Patent•
12 Sep 1979TL;DR: In this article, a lactic-glycolic copolymers having molecular weights of about 6000 to about 35000 are prepared by condensation of lactic acid and glycolic acid in the presence of readily removable strong acid ion exchange resins.
Abstract: Lactic-glycolic copolymers having molecular weights of about 6000 to about 35000 are prepared by condensation of lactic acid and glycolic acid in the presence of readily removable strong acid ion-exchange resins.
74 citations
TL;DR: Clofilium is the most promising member in a new series of antifibrillatory agents to selectively prolong cardiac action potential duration (APD) and effective refractory period (ERP) and in normal superfused canine Purkinje fibers, cl ofilium prolonged APD and ERP by a maximum of 35%.
53 citations
TL;DR: The data suggest that the Na+‐independent binding of [3H]GABA in the Triton‐treated cerebellar membranes represents the synaptic receptors of GABA.
Abstract: — The treatment of cerebellar membranes of rat brain with a low concentration of Triton X-100 followed by sufficient washing results in an increase of the Na+-independent binding of [3H]GABA and a total loss of the Na +-dependent binding of [3H]GABA. The Na+-independent binding of [3H]GABA was more abundant in membranes of cerebellum than in membranes of other rat brain regions and mainly localized in the synaptic membrane fraction of a cerebellar homogenate. In the Triton-treated membranes, the Na+-independent binding of [3H]GABA was a saturable process, which could be resolved into two components, a high and a low affinity component with dissociation constants of 4.5 and 30 nm, respectively. The neurophysiological agonists, muscimol, GABA, and imidazole acetic acid, and the antagonist, bicuculline, inhibited the high affinity Na+-independent binding of [3H]GABA by 50% at 0.003, 0.012, 0.3 and 10 μm respectively. These data suggest that the Na+-independent binding of [3H]GABA in the Triton-treated cerebellar membranes represents the synaptic receptors of GABA. It is emphasized that extensive washing of the membranes after a Triton treatment is necessary in order to detect the high affinity Na+-independent binding of [3H]GABA.
48 citations
Patent•
09 Oct 1979TL;DR: In this paper, Syn-7-(2-amino-4-thiazolyl)-(methoxyimino)-acetamido-3-acetoxymethyl,3-cephem-4 carboxylic acid is isolated by formation of cyclic ether solvates.
Abstract: Syn-7-(2-amino-4-thiazolyl)-(methoxyimino)-acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid is isolated by formation of cyclic ether solvates.
46 citations
TL;DR: Its blood pressure-lowering activity in both types of rats was more potent than that of lergotrile, a weaker dopamine agonist, and the involvement of dopaminergic mechanisms in maintaining the homeostasis of blood pressure and perhaps in the pathology of hypertension such as that in spontaneously hypertensive rats.
TL;DR: The combination of fluoxetine and 5-HTP significantly lowered blood pressure in spontaneously hypertensive rats and in rats made hypertensive by treatment with deoxycorticosterone and saline.
TL;DR: Metergoline antagonized the elevation of serum corticosterone by quipazine in rats and may have occurred at receptors that are not serotonin receptors or that represent a subset of serotonin receptors not mediating the actions of serotoninergic agents other than quipazines.
Abstract: Metergoline antagonized the elevation of serum corticosterone by quipazine in rats. The ED50 of metergoline was less than 0.1 mg/kg, ip, and the effects of a 3 mg/kg dose persisted for more than 24 h. Metergoline did not antagonize the elevation of serum corticosterone by theophylline or ketamine {i.e. did not prevent corticosterone release nonspecifically) and did not affect the concentration of quipazineMn the brain. Since quipazine is a serotonin receptor agonist, the antagonistic effects of metergoline may have been due to competition with quipazine at serotonin receptor sites in the brain. Some other agents capable of blocking serotonin receptors also antagonized the elevation of serum corticosterone by quipazine. These included LY53857, which gave complete blockade at 3 mg/kg, and cyproheptadine and spiperone, which gave significant but incomplete antagonism at 1 mg/kg. Methysergide at 3 mg/kg did not alter the effect of quipazine. Metergoline did not antagonize the elevation of serum corticosterone...
TL;DR: Observations suggest that cardiac conduction depression may be a factor in some of the cardiac toxicities associated with propoxyphene overdosage.
Patent•
21 Nov 1979TL;DR: Optically active N-3-(4-substituted phenyl)propyl-β-phenethanolamines are provided as well as pharmaceutical compositions containing such compounds.
Abstract: Optically active N-3-(4-substituted phenyl)propyl-β-phenethanolamines are provided as well as pharmaceutical compositions containing such compounds. A method for effecting weight control in obese animals utilizing optically active phenethanolamines is disclosed. Novel intermediates useful in the preparation of optically active β-phenethanolamines are provided.
Patent•
05 Feb 1979TL;DR: 6n-n-Propyl (ethyl or allyl)-8β-methoxy-(methylsulfinyl, methylsulfonyl, or methylmercapto) methylergolines, 8-ergolenes or 9-ergorenes, useful as prolactin inhibitors and in the treatment of Parkinsonism.
Abstract: 6-n-Propyl (ethyl or allyl)-8β-methoxy-(methylsulfinyl, methylsulfonyl, or methylmercapto) methylergolines, 8-ergolenes or 9-ergolenes, useful as prolactin inhibitors and in the treatment of Parkinsonism.
TL;DR: Flock immunity, as determined by immunity challenge, was equivalent between the control strain and the higher dosages of Wis-F-125, and the Wis- F-96 strain did not adequately immunize chickens in these experiments.
Patent•
12 Oct 1979TL;DR: The 7-acylamido-3-halo cephalosporin acids and pharmaceutically acceptable esters provided are valuable antibiotic compounds having desirable therapeutic properties.
Abstract: 7-Acylamido- and 7-amino-3-halo-3-cephem-4-carboxylic acids, esters and pharmaceutically-acceptable salts and esters thereof are new cephalosporin compounds provided by the reaction of a 7-acylamido-3-hydroxy-3-cephem-4-carboxylic acid ester or a 7-amino-3-hydroxy-3-cephem-4-carboxylic acid ester with an iodinating, fluorinating, chlorinating, or brominating reagent. For example, 7-amino-3-chloro-3-cephem-4-carboxylic acid and 7-phenoxyacetamido-3-chloro-3-cephem-4-carboxylic acid are provided. The 7-acylamido-3-halo cephalosporin acids and pharmaceutically acceptable salts and esters provided are valuable antibiotic compounds having desirable therapeutic properties.
Patent•
19 Apr 1979TL;DR: Octahydropyrazolo[3,4g]quinolines, dopamine agonists, useful in treatment of Parkinsonism and in inhibiting secretion of prolactin this paper.
Abstract: Octahydropyrazolo[3,4-g]quinolines, dopamine agonists, useful in treatment of Parkinsonism and in inhibiting secretion of prolactin
TL;DR: The results support the hypothesis that these peptides serve as neurotransmitters in the striatum, but autoregulation of their release by morphine and naloxone could not be demonstrated.
TL;DR: In this article, the optical rotatory properties of β-lactam structures are calculated using semi-empirical Extended Huckel and CNDO wavefunctions. But the results of the spectral analysis are limited.
Patent•
06 Feb 1979TL;DR: In this paper, a method of treating hypertension using 9-amino derivatives of 1-hydroxy-3-substituted-tetrahydro and hexahydrodibenzo[b,d]pyrans is described.
Abstract: 1-Hydroxy-3-substituted-tetrahydro and hexahydrodibenzo[b,d]pyrans having an amino group or amino derivative at the 9-position are useful as analgesics, anti-depressants, anti-anxiety agents, hypotensive agents, and intermediates. Pharmaceutical formulations containing such 9-amino derivatives are provided, as well as a method of treating hypertension.
TL;DR: Three compounds evaluated for dopaminergic properties induced emesis in dogs, contralateral circling in unilaterally lesioned rats, and inhibited prolactin secretion and were weak inhibitors of 3-H-dopamine binding in calf caudate homogenates.
Patent•
02 Jul 1979TL;DR: In this paper, the authors describe a class of compounds known as aminocarbonyl compounds, which are useful in the weight control of mammals and are known to have the S absolute stereochemical configuration.
Abstract: Compounds of the formula (I):
wherein:
R 1 is hydrogen or fluorine; R 2 is methyl or ethyl; R, is hydroxy, C 1 -C 4 alkanoyloxy, aminocarbonyl. methylaminocarbonyl or C 1 -C 2 alkoxycarbonyl; C is an asymmetric carbon atom having the R absolute stereochemical configuration; and C is an asymmetric carbon atom having the S absolute stereochemical configuration;
and pharmaceutically-acceptable salts thereof, are useful in the weight control of mammals.
TL;DR: This series of studies indicates that Mif-I does not act directly on the striatal dopamine postsynaptic receptor under the conditions tested, although it is possible that MIF-I could act indirectly at this or another site in vivo by releasing or activating some other factor.
Patent•
05 Feb 1979TL;DR: In this article, the ergoline compounds of the following formula are described: wherein R1 is ethyl, n-propyl, or allyl; Y is O, S, SO, or SO2; X is hydrogen, chloro, or bromo; the dotted line represents the optional presence of a double bond; and the pharmaceutically acceptable acid addition salts thereof.
Abstract: Novel ergoline compounds of the following formula are described: wherein R1 is ethyl, n-propyl, or allyl; Y is O, S, SO, or SO2; X is hydrogen, chloro, or bromo; the dotted line represents the optional presence of a double bond; and the pharmaceutically-acceptable acid addition salts thereof. The compounds are useful to inhibit prolactin secretion or to treat Parkinson's syndrome.
TL;DR: It is found that MIF-I does not alter the turnover rate of DA in nigrostriatal neurons, and it is possible that Mif-I or some substance released by M IF-I acts at a postsynaptic receptor site.
TL;DR: VDS has a similar activity to VCR against the P 388 leukemia, the P 1534 (J) (sc) leukemia, and the CA-755 mammary carcinoma, and increased the median survival and lifespan of mice with B-15 melanoma to a greater extent than VCR and VBL.
Abstract: VDS is a new semisynthetic vinca alkaloid, which can be prepared either from VBL sulfate or from desacetylvinblastine (B 2, H 1). It has a wider spectrum of antitumor activity than VBL in animal tumor test systems, and a toxicity somewhere between that of VCR and that of VBL [38, 41]. According to the structural formula of VDS (23 amino -4-deacetoxy-23 demethoxy-4-hydroxy-vincaleucoblastine sulfuric acid salt), the C-23 position of VDS has an amino group instead of the methoxy group in VBL, and the C-4 position of VBL is deacetylated and bears a hydroxy group in the VDS molecule. In contrast to VCR, the N-linked substituent in the vindoline portion of VDS and of VBL is a methyl group, and not a formyl group as in VCR. Despite the minimal chemical differences within the vinca derivatives a high stereochemical specificity is required for specific antitumor activity: in the Ridgeway osteogenic sarcoma and in the Gardener lymphosarcoma the following order of antineoplastic activity was observed [1]. VCR; Vindesine=deacetylvinblastinehydrazide; Deacetylvinblastine; Dihydrovindesine; C-18-Decarbomethoxyvindesine; VBL. VDS has a similar activity to VCR against the P 388 leukemia, the P 1534 (J) (sc) leukemia, and the CA-755 mammary carcinoma. VDS increased the median survival and lifespan of mice with B-15 melanoma to a greater extent than VCR and VBL. VDS, like VCR and VBL, showed almost no activity against the L 1210 leukemia and against the Lewis lung carcinoma [1]. The apparent structure-activity relationship is paralleled by a structure-toxicity relationship among the
01 Jan 1979
TL;DR: In this article, the authors present a diagrammatic illustration of the fermentation process and emphasize on the economic significance of several fermentation process improvement strategies to evaluate alternative approaches to evaluate the time course of nutrient use for penicillin fermentation.
Abstract: Publisher Summary The process used for the production of penicillin by fermentation is quite complex and involves culture maintenance, fermentation, and extraction/purification procedures. This chapter presents a diagrammatic illustration of that process and emphasizes on the economic significance of several fermentation process improvement strategies to evaluate alternative approaches. The chapter discusses about the time course of nutrient use for penicillin fermentation. Many factors influence the cost of penicillin production. Even the age of the facility can have a significant influence. Many large scale facilities are 15 to 20 years old and the fixed charges are much reduced. If the fixed charges drop by $200 (out of a $378 total), the unit cost becomes $1454.41/89.23 Kg = $1630/Kg, substantially less than the standard of $18.54/Kg. Maintenance would increase and the labor tends to be higher in older plants which often have smaller fermenters, greater contamination, and less efficient process strategies. The choice among development alternatives depends upon the scale of production and the importance of a given product among a group of similar products which the process improvement team might work on.
Patent•
14 Feb 1979TL;DR: In this article, the authors present a novel anticoccidial compositions and methods of employing the same to control coccidiosis in poultry, which comprise a polyether antibiotic and a second component selected from nicarbazin and 4,4'-dinitrocarbanilide.
Abstract: The present invention is directed to novel anticoccidial compositions and methods of employing the same to control coccidiosis in poultry. These compositions comprise a polyether antibiotic and a second component selected from nicarbazin and 4,4'-dinitrocarbanilide.