Abstract: A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the steps of reacting methylergometrine with a brominating agent to produce [(1S)-1-(Hydroxymethyl)propylamino][(6aR,9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde as a first intermediate, and then hydrolyzing [(1S)-1-(Hydroxymethyl)propylamino][(6aR,9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde to yield bromo-lysergic acid as a second intermediate, wherein bromo-lysergic acid is then amidated to yield 2-bromo-LSD or a salt or hydrate thereof.

Abstract: Provided herein are ergoline compounds and pharmaceutical compositions thereof. In some embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1A, 5-HT1B and 5-HT1D receptors without agonizing the 5-HT2B receptor using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HT2B adrenergic alpha2A and/or the alpha2B receptors using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the D2 and D3 receptor using the compounds and pharmaceutical compositions disclosed herein.

Abstract: Provided herein are ergoline compounds and pharmaceutical compositions thereof. In some embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1A, 5-HT1B and 5-HT1D receptors without agonizing the 5-HT2B receptor using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HT2B adrenergic alpha2A and/or the alpha2B receptors using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the D2 and D3 receptor using the compounds and pharmaceutical compositions disclosed herein.

Abstract: Compounds, e.g., of formula (I) and (Ia), pharmaceutical compositions comprising the compounds and methods of using the compounds and pharmaceutical compositions for treating pain disorders, e.g., disorders associated with cephalic pain, are provided.

Abstract: Provided herein are novel cabergoline analogs and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HT2B receptor and 5-HT2C receptors the using the compounds and compositions disclosed herein.

Abstract: Provided herein are novel methysergide derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders or symptoms thereof, such as, migraine and Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein, such as, for example, are methods for antagonizing the 5-HT2B receptor without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein such as, for example, are methods of agonizing the 5-HT1A receptor using the compounds and compositions disclosed herein.

Abstract: Provided herein are novel fluoroergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2B receptors using the compounds and compositions disclosed herein.

Abstract: Provided herein are novel fluoroergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2B receptors using the compounds and compositions disclosed herein.

Abstract: Provided herein are novel methysergide derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders or symptoms thereof, such as, migraine and Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein, such as, for example, are methods for antagonizing the 5-HT2B receptor without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein such as, for example, are methods of agonizing the 5-HT1A receptor using the compounds and compositions disclosed herein.

Abstract: Compounds, e.g., of formula (I) and (Ia), pharmaceutical compositions comprising the compounds and methods of using the compounds and pharmaceutical compositions for treating pain disorders, e.g., disorders associated with cephalic pain, are provided.

Abstract: Provided herein are novel methysergide derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders or symptoms thereof, such as, migraine and Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein, such as, for example, are methods for antagonizing the 5-HT2B receptor without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein such as, for example, are methods of agonizing the 5-HT1A receptor using the compounds and compositions disclosed herein.

Abstract: The present invention relates to a veterinary anti-prolactin composition to be administered to ruminants. Said composition includes at least one anti-prolactin compound which is an agonist for dopamine receptors and which is particularly useful for preventing and/or reducing the harmful effects in ruminants linked to use for a shortened dry period. Said composition is particularly useful for preventing and/or reducing metabolic diseases and/or reproductive disorders when lactation is resumed.

Abstract: Provided herein are novel cabergoline analogs and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HT2B receptor and 5-HT2C receptors the using the compounds and compositions disclosed herein.

Abstract: The present invention relates to a cabergoline crystal form L, its preparation from halogenated aromatic solvents and aliphatic hydrocarbons and to pharmaceutical compositions containing the new form.

Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo. An example is: 6-n-propyl-8?-ergolinglmethylthioacetyl-D-Phe-c(Cys-Tyr-D-Trp-Lys-Abu-Cys)-Thr-NH2.

Abstract: The present invention relates to a method for preparing microbiologically produced ergot alkaloids of the following formula (I), comprising the step of: a) extracting the fermentation product occurring during the biological production, said product containing at least one ergot alkaloid of formula (I), at a pH of 8-14 using an extractant with a solubility in water of 0.2 g/100 g of water to 25 g/100 g water at 20° C., wherein the amount of extractant is sufficient to form a 2-phase system together with the fermentation product.

Abstract: This invention relates to a new and efficient process for the production of dopamine agonists such as Cabergoline and the intermediates thereof.

Abstract: A process for preparing cabergoline (I) from ergoline-8?-carboxylic acid ester (XIII) comprising the following steps. (XIII), (XVI), (XVII), (XVIII), (XIX), (I). The present case also relates to the intermediates (XVI), (XVII), (XVIII) and (XIX) as well as the polymorphic amorphous form of Cabergoline (I) and the production thereof.

Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo.

Abstract: The present invention relates to a cabergoline crystal form L, its preparation from halogenated aromatic solvents and aliphatic hydrocarbons and to pharmaceutical compositions containing the new form.

Abstract: Disclosed are ergoline derivatives, Formula (I), wherein either each of R1 and R2, independently, is H; optionally R10 and/or R11-substituted-phenyl or -phenyl-C1-4alkyl; optionally R10 and/or R11-substituted-heteroaryl or -heteroaryl-C1-4alkyl; optionally R10 and/or R11-substituted heteroaryl N-oxide; optionally R10-substituted C1-C8 alkyl; optionally R10-substituted C2-C8 alkenyl, optionally R10-substituted C2-C8 alkynyl; optionally R10-substituted C3-C8 cycloalkyl, or optionally R10-substituted C4-C8 cycloalkenyl; or R1 and R2 form together with the nitrogen atom to which they are attached an optionally R10-substituted 3-8 membered ring containing in addition to the nitrogen atom up to 2 heteroatoms selected independently from N, O and S; R3 is H; OR1; CH2R1R2; (CH2)1-2NR1R2; CH2—CH2—OR1; CH2—CO—NR1R2; or CO—CH2R1R2; R4 is F; Cl; Br; I; OR1; NR1R2 or has one of the significances given for R1; and R5 has one of the significances given for R1, in free form or in salt form for preventing or treating disorders

Abstract: Compounds, e.g., of formula (I) and (Ia), pharmaceutical compositions comprising the compounds and methods of using the compounds and pharmaceutical compositions for treating pain disorders, e.g., disorders associated with cephalic pain, are provided.

Abstract: Provided are new crystalline Forms VIII, IX, XI, XII, XIV, XV, XVI, XVII, and XVIII of cabergoline. Also provided are novel processes for preparation of cabergoline Form I, Form II, Form VII, and amorphous cabergoline.

Abstract: Disclosed are ergoline derivatives, Formula (I), wherein either each of R1 and R2, independently, is H; optionally R10 and/or R11-substituted-phenyl or -phenyl-C1-4alkyl; optionally R10 and/or R11-substituted-heteroaryl or -heteroaryl-C1-4alkyl; optionally R10 and/or R11-substituted heteroaryl N-oxide; optionally R10-substituted C1-C8 alkyl; optionally R10-substituted C2-C8 alkenyl, optionally R10-substituted C2-C8 alkynyl; optionally R10-substituted C3-C8 cycloalkyl, or optionally R10-substituted C4-C8 cycloalkenyl; or R1 and R2 form together with the nitrogen atom to which they are attached an optionally R10-substituted 3-8 membered ring containing in addition to the nitrogen atom up to 2 heteroatoms selected independently from N, O and S; R3 is H; OR1; CH2R1R2; (CH2)1-2NR1R2; CH2—CH2—OR1; CH2—CO—NR1R2; or CO—CH2R1R2; R4 is F; Cl; Br; I; OR1; NR1R2 or has one of the significances given for R1; and R5 has one of the significances given for R1, in free form or in salt form for preventing or treating disorders

Abstract: This invention relates to a new and efficient process for the production of dopamine agonists such as Cabergoline and the intermediates thereof.

Abstract: A method of preparing cabergoline Form I, comprising forming a solvate including cabergoline and a p-disubstituted benzene of formula (A) or 1,3,5-trimethylbenzene and obtaining cabergoline Form I from the solvate. Another aspect of the present invention provides a method for preparing cabergoline Form I comprising dissolving cabergoline in p-disubstituted benzene or 1,3,5-trimethylbenzene and recovering the cabergoline Form I polymorph, suitably by direct crystallization of Form I or by recovery of a solvate which can be converted to Form I. Another aspect of the present invention provides a novel cabergoline polymorph designated cabergoline Form FB and a method of preparing said polymorph by dissolving or forming a solvate of cabergoline in fluorobenzene and recovering cabergoline Form FB.

Abstract: A method of preparing cabergoline Form I, comprising forming a solvate including cabergoline and 4-fluorotoluene or 1,3,5-trimethylbenzene and obtaining cabergoline Form I from the solvate. Another aspect of the present invention provides a method for preparing cabergoline Form I comprising dissolving cabergoline in 4-fluorotoluene or 1,3,5-trimethylbenzene and recovering the cabergoline Form 1 polymorph. Cabergoline Form I can then be obtained from the solution, suitably by direct crystallization of Form I or by recovery of a solvate which can be converted to Form I.

Abstract: A process for making cabergoline uses silyl-protecting agents to protect the indole nitrogen atom.

Abstract: The present invention discloses a method for preparing cabergoline form I by combining cabergoline and a solvent comprising ethylbenzene to form a solvate and obtaining form I from the solvate. Also disclosed in a method for preparing cabergoline form I by combining cabergoline and a first solvent to form a solution and additionally including a second solvent to the solution, followed by crystallization to form cabergoline form I. Further disclosed is a solvate form of cabergoline comprising cabergoline and ethylbenzene and, optionally, n-heptane.

Abstract: The invention provides a hapten derivatized with a crosslinker at the nitrogen of the 8?-carboxamide of 2-oxo-3-hydroxy LSD. The invention also provides an immunogen comprising the aforementioned hapten coupled to an antigenicity-conferring carrier material; a conjugate comprising the aforementioned hapten coupled to a labelling agent, as well as, antibodies raised against the aforementioned immunogen and capable of binding with at least the 3-hydroxy-2-pyrrolidone structural epitope of 2-oxo-3-hydroxy LSD.

Abstract: The invention provides methods for preparing amorphous physical form of cabergoline, and solvate form A of cabergoline useful in the preparation of the first mentioned physical form. A method for treating a prolactin disorder with medicaments prepared from amorphous physical form of cabergoline and solvate form A of cabergoline is also disclosed.

Abstract: A process for the synthesis of pergolide (Formula (I)) (D-6-n-propyl-8?methylmercaptomethylergo line) from acid 9,10-dihydrolysergic is herein disclosed. The process can be carried out without isolating most intermediates and is particularly convenient both from the yield and safety standpoint.

Abstract: A process for producing crystalline form I of cabergoline, which process comprises crystallization of the desired form from a toluene/diethyl ether mixture comprising raw cabergoline, followed by recovery and drying of the resulting crystals. A new solvate form V of cabergoline, useful as an intermediate, is also provided.

Abstract: Compounds of the general structural formula and use of the compounds and salts and solvates thereof, as therapeutic agents.

Abstract: Crystalline form II of cabergoline, a pharmaceutical composition containing it and a process for its preparation are disclosed. The process may comprise crystallization from s solution of raw cabergoline in an organic solvent at low temperatures or submitting to a slurry procedure a mixture of cabergoline forms I and II in a solvent at a temperature below 30° C.

Abstract: The present invention provides hapten derivatives useful for the preparation of antigens, antibodies and reagents for use in immunoassays for the detection of LSD and 2-oxo-3-hydroxy LSD. In the present invention, the 2-oxy LSD nucleus is derivatized out of the indole nitrogen to form an aminoalkyl derivative. The resulting haptens can then be further modified at this functionalized position for linking to appropriate immunogenic or labeling groups to provide reagents for immunoassays having substantially equal specificity for both LSD and 2-oxo-3-hydroxy-LSD.

Abstract: A process for producing crystalline form I of cabergoline, which process comprises crystallization of the desired form from a toluene/diethyl ether mixture comprising raw cabergoline, followed by recovery and drying of the resulting crystals. A new solvate form V of cabergoline, useful as an intermediate, is also provided.

Abstract: A process for preparation of N-(ergoline-8&bgr;-carbonyl)ureas of the formula [I] their stereoisomers as well as acid addition salts thereof which process comprises silylating an ergoline-8&bgr;-carboxamide of the formula [2], their stereoisomers as well as metal or ammonium salts or acid addition salts thereof and reacting the resultant product with an isocyanates R1N═C═O [5] wherein R1 is selected from alkyl having from 1 to 4 carbon atoms, cyclohexyl, phenyl, and dimethylamino alkyl group —(CH2)nNMe2 in which n is an integer, R2 is selected from hydrogen, alkyl having from 1 to 4 carbon atoms, cyclohexyl, phenyl, dimethylamino alkyl group —(CH2)nNMe2 in which n is an integer, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazolyl or thiadiazolyl, R3 represent a hydrocarbon group having from 1 to 4 carbon atoms, and R4 is selected from hydrogen, halogen, methylthio and phenylthio group;; followed by desilylation.

Abstract: Crystalline form VII of cabergoline, a pharmaceutical composition containing it and a process for its preparation are disclosed. The process may comprise a slurry procedure using form I or mixture of forms I and VII of cabergoline in a solvent at a temperature above 30° C.

Abstract: Crystalline form II of cabergoline, a pharmaceutical composition containing it and a process for its preparation are disclosed. The process may comprise crystallization from a solution of raw cabergoline in an organic solvent at low temperatures or submitting to a slurry procedure a mixture of cabergoline Forms I and II in a solvent at a temperature below about 30° C.

Abstract: A process for producing crystalline form I of cabergoline, which process comprises crystallization of the desired form from a toluene/diethyl ether mixture comprising raw cabergoline, followed by recovery and drying of the resulting crystals. A new solvate form V of cabergoline, useful as an intermediate, is also provided.

Abstract: The invention provides a hapten derivatised with a crosslinker at the nitrogen of the 8&bgr;-carboxamide of 2-oxo-3-hydroxy LSD. The invention also provides an immunogen comprising the aforementioned hapten coupled to an antigenicity-conferring carrier material; a conjugate comprising the aforementioned hapten coupled to a labelling agent, as well as, antibodies raised against the aforementioned immunogen and capable of binding with at least the 3-hydroxy-2-pyrrolidone structural epitope of 2-oxo-3-hydroxy LSD.

Abstract: To improve the detection of LSD, and LSD metabolites in biological samples, antibodies are raised to 2-oxo-3-hydroxy-LSD conjugated to a protein carrier. Selected antibodies are matched with an immunoassay reagent in which the 2-oxo-3-hydroxy-LSD is conjugated in the same position to a labeling or separation means. The set of reagents can be used in immunoassays for detecting or confirming the presence of LSD or LSD metabolites in a sample potentially containing interfering substances.

Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigens, antibodies and reagents having superior performance characteristics for use in immunoassays for the detection of LSD and nor-LSD. In the present invention the LSD nucleus is derivatized out of the indole nitrogen to form an aminoalkyl derivative. Derivatives have also been synthesized out of the piperidine nitrogen of the LSD nucleus. The resulting haptens can then be further modified at these functionalized positions for linking to appropriate antigenic or labelling groups to provide reagents for LSD immunoassays having excellent sensitivity and selectivity for both LSD and nor-LSD.

Abstract: The invention relates to novel substituted 2-amino-4-alkylamino-1,3,5-triazines of the formula (I) in which R1 represents in each case optionally substituted alkyl having 2 to 6 carbon atoms or cycloalkyl having 3 to 6 carbon atoms, R2 represents hydrogen or represents alkyl having 1 to 4 carbon atoms, A represents oxygen or methylene, Ar represents in each case optionally substituted phenyl, naphthyl or heterocyclyl, and Z represents hydrogen, represents halogen or represents in each case optionally substituted alkyl, alkoxy, alkylcarboxyl, alkoxycarbonyl, alkylthio, alkylsulphinyl, alkylsulphonyl, alkenyl or alkinyl, to processes and to novel intermediates for their preparation and to their use as herbicides.

Abstract: The present invention relates to a method for the synthesis of the dihydroindole C-ring found in CC-1065/duocarmycin analogs.

Abstract: Novel chemical analogs are disclosed for the essential heroin metabolite 6-O-acetyl morphine (6MAM). The analogs optionally can be made to contain protein reactive groups, and can be used to form protein conjugates, fluorescently labeled compounds, and solid-phase adsorbants. The proteins conjugates can be used in turn to raise antibodies reactive with 6MAM and having a low cross-reactivity with the closely related opiates, morphine and codeine. The antibodies can be used in combination with labeled analogs in exquisitely sensitive immunoassays suitable for testing for heroin abuse.

Abstract: The present invention relates to a novel process for preparing lysergic acid by isomerizing paspalic acid, using a tetraalkylammonium hydroxide.

Abstract: Novel compounds of Formula (7.0a), (7.0b) or (7.0c): ##STR1## are disclosed. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering a compound of the formula (7.0a), (7.0b) or (7.0c) to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being.

Abstract: A method of treating psychosis including administering an antipsychotically effective amount of an ergolinyl derivative of 2-propinylamine of the formula I ##STR1## wherein, R.sub.1, R.sub.2, and R.sub.3 independently represent a hydrogen atom or a straight-chain or branched-chain C.sub.1 -C.sub.6 alkyl group, X represents a hydrogen or a halogen atom, Z represents a carbonyl or methylene group, and C.sub.9 - - - -C.sub.10 represents a single or a double, diastereomeric forms, racemates and acid addition salts thereof.