NOVEL ISO-ERGOLINE DERIVATIVES

Provided herein are novel iso-ergoline 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-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor 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 alphaand/or the alphareceptors using the compounds and compositions disclosed herein. 2. The compound of claim 1 , wherein Ris hydrogen or (C-C) alkyl substituted with one or more fluorine atoms claim 1 , n is 0 claim 1 , Ris hydrogen or (C-C) alkyl claim 1 , Ris substituted alkyl or —NRR claim 1 , Ris methyl substituted with one or more fluorine atoms and Ris hydrogen claim 1 , substituted alkyl claim 1 , substituted acyl or —CONRR.3. The compound of claim 1 , wherein Ris hydrogen claim 1 , methyl or methyl substituted with one or more fluorine atoms claim 1 , Ris alkyl claim 1 , halo claim 1 , —OR claim 1 , n is 1 claim 1 , Ris hydrogen claim 1 , methyl or allyl claim 1 , Ris substituted alkyl or —NRR claim 1 , Ris methyl substituted with one or more fluorine atoms and Ris hydrogen claim 1 , substituted alkyl claim 1 , substituted acyl or —CONRR.4. The compound of claim 1 , wherein Ris hydrogen claim 1 , methyl or methyl substituted with one or more fluorine atoms claim 1 , n is 0 claim 1 , Ris hydrogen claim 1 , methyl or allyl claim 1 , Ris substituted alkyl or —NRR claim 1 , Ris methyl substituted with one or more fluorine atoms and Ris hydrogen claim 1 , substituted alkyl claim 1 , substituted acyl or —CONRR.9. The compound of claim 1 , wherein Ris hydrogen claim 1 , n is 0 claim 1 , Ris allyl claim 1 , Ris —NRRor ...

Lisuride, Terguride and Derivatives Thereof for Use in the Prophylaxis and/or Treatment of Fibrotic Changes

The present invention relates to the use of 5-HTreceptor antagonists and in particular of 8-α-ergolines such as lisuride, terguride and the derivatives thereof as 5-HTand 5-HTreceptor antagonists and antioxidants in preferably higher-dosed and preferably continuous use for the treatment, progression prophylaxis and general prophylaxis of organ fibroses and other pathological organ remodeling caused by mesenchymal proliferation 2. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to for extending the life of the organism.3. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 1 , whereby during the treatment time claim 1 , at least 80% of the time claim 1 , preferably at least 100% of the treatment time claim 1 , the 5-HT- and/or 5-HT-receptor occupancy in the target organ is at least 90%.4. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 3 , whereby during the entire treatment time claim 3 , the 5-HT- and/or 5-HT-receptor occupancy in the target organ is complete.5. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 1 , whereby the active ingredient level in the systemic circulation of the organism during the treatment time claim 1 , at least 80% of the time claim 1 , preferably 100% of the time continuously claim 1 , is at least 5 pg/ml claim 1 , more preferably at least 100 pg/ml claim 1 , more preferably at least 200 pg/ml claim 1 , and most preferably 300-500 pg/ml.6. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 1 , wherein the administration is carried out at a dose of 0.01 to 5.0 mg per day claim 1 , preferably 0.15 to 3.0 mg per day claim 1 , and most preferably 0.25 to 1.0 mg per day.7. Lisuride or ...

Novel fluoroergoline analogs

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-HT 1D and/or the 5-HT 1B receptor, without agonizing the 5-HT 2B 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 alpha 2A and/or the alpha 2B receptors using the compounds and compositions disclosed herein.

NOVEL ISO-ERGOLINE DERIVATIVES

Provided herein are novel iso-ergoline 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-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor 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 alphaand/or the alphareceptors using the compounds and compositions disclosed herein. 214-. (canceled)16. The method of claim 15 , wherein the compound selectively agonizes the 5-HTreceptor over the 5-HTreceptor in a ratio of about 4:1.17. The method of claim 15 , wherein the compound selectively agonizes the 5-HTreceptor over the 5-HTreceptor in a ratio of about 30:1.1924-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/531,416, filed Jun. 22, 2012 which claims priority under 35 U.S.C. §119(e) from U.S. Provisional Application Ser. No. 61/577,563, filed Dec. 19, 2011, which are hereby incorporated by reference in their entirety.Provided herein are novel isoergoline 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, 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-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor 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 alphaand/or ...

NITROGENATED AROMATIC HETEROCYCLIC DERIVATIVE AND ORGANIC ELECTROLUMINESCENT ELEMENT USING SAME

A nitrogen-containing aromatic heterocyclic derivative in which a nitrogen atom of an indenocarbazole skeleton optionally having a hetero atom or an indenoindole skeleton optionally having a hetero atom is bonded to a dibenzofuran or a dibenzothiophene directly or indirectly. The derivative realizes an organic EL device with a high emission efficiency and a long lifetime. 2: The aromatic heterocyclic derivative according to claim 1 , whereinW of formulae (1-1) and (1-2) represents a single bond, andZ of formulae (1a) and (1b) represents a single bond.7: The aromatic heterocyclic derivative according to claim 1 , wherein Lrepresents a single bond.9. (canceled)10: The aromatic heterocyclic derivative according to claim 1 , wherein X represents an oxygen atom.11: The aromatic heterocyclic derivative according to claim 1 , wherein X represents a sulfur atom.12: The aromatic heterocyclic derivative according to claim 1 , wherein X represents CRR.13: The aromatic heterocyclic derivative according to claim 1 , wherein X represents SiRR.14: The aromatic heterocyclic derivative according to claim 1 , wherein Y represents an oxygen atom.15: The aromatic heterocyclic derivative according to claim 1 , wherein Y represents a sulfur atom.16: The aromatic heterocyclic derivative according to claim 1 , wherein Lis bonded to a carbon atom at 4-position of the structure represented by formula (1c).17. A material for organic electroluminescence device claim 1 , comprising the aromatic heterocyclic derivative according to .18: A hole transporting material for organic electroluminescence device claim 1 , comprising the aromatic heterocyclic derivative according to .19: An organic electroluminescence device claim 1 , comprising:a light emitting layer, andorganic thin film layers between an anode and a cathode,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein at least one of the organic thin film layers comprises the aromatic heterocyclic derivative according to .'}20: The ...

Composition and Method for Treating Metabolic Disorders

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects. 126.-. (canceled)27. A method for therapeutically modifying and resetting the central circadian rhythm of dopaminergic activity of a vertebrate , comprising administering to said vertebrate bromocriptine citrate.28. The method of which comprises administering bromocriptine citrate at a time of day that will increase central dopaminergic activity of the patient at the time of day the circadian peak of central dopaminergic activity in a healthy individual of the same species and sex.29. The method of which comprises administering bromocriptine citrate at a time of day that will increase central dopaminergic activity of the patient within four hours of the circadian peak of central dopaminergic activity in a healthy individual of the same species and sex.30. The method of wherein the resetting step comprises adjusting the central circadian rhythm of dopaminergic activity of a vertebrate to approximate the circadian peak dopaminergic activity of a healthy individual of the same species and sex.31. The method of wherein said bromocriptine ...

Composition and Method for Treating Metabolic Disorders

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects. 1. Bromocriptine citrate.2. A pharmaceutical dosage form comprising bromocriptine citrate.3. A pharmaceutical dosage form comprising bromocriptine citrate and pharmaceutically acceptable excipients.4. The pharmaceutical dosage form of comprising an oral dosage form.5. The pharmaceutical dosage form of further comprising a low moisture content filler claim 2 , a water-scavenging agent or a lubricant.6. The pharmaceutical dosage form of further comprising at least one excipient that affects the rate of bromocriptine citrate release from said dosage form.7. The pharmaceutical dosage form of further comprising a disintegrating agent.8. The pharmaceutical dosage form of further comprising at least one of cornstarch claim 2 , mannitol claim 2 , colloidal silicon dioxide or stearic acid.9. The pharmaceutical dosage form of comprising between about 0.05 μg and about 0.5 mg/kg of body weight of bromocriptine citrate.10. The pharmaceutical dosage form of further comprising citric acid.11. The pharmaceutical dosage form of further comprising ...

FLUOROERGOLINE DERIVATIVES AND USES THEREOF

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-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor 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 alphaand/or the alphareceptors using the compounds and compositions disclosed herein. 1. A fluoroergoline derivative composition suitable for use in the treatment of a disease , condition , or disorder selected from the group consisting of migraine , amyotrophic lateral sclerosis (ALS) , Parkinson's disease , stress/anxiety , nausea , emesis , aggression , pain , neuropathic pain , sleeplessness , insomnia , restless leg syndrome and depression.3. The composition of claim 2 , wherein the fluoroergoline derivative is in the form of a pharmaceutically acceptable salt claim 2 , solvate claim 2 , ester or hydrate.4. The composition of claim 3 , wherein the fluoroergoline derivative is in the form of a solid.5. The composition of claim 4 , wherein the composition is suitable for buccal administration.6. The composition of claim 4 , wherein the fluoroergoline derivative is in the form of amorphous claim 4 , semi-crystalline or crystalline particles.7. The composition of claim 6 , wherein the amorphous claim 6 , semi-crystalline or crystalline particles are suitable for administration via inhalation.8. The composition of claim 1 , wherein the composition comprises a pharmaceutically acceptable vehicle.9. The composition of claim 1 , wherein the composition comprises a pharmaceutically acceptable excipient.10. The composition ...

Novel methysergide derivatives

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-HT 2B receptor without agonizing the 5-HT 2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein such as, for example, are methods of agonizing the 5-HT 1A receptor using the compounds and compositions disclosed herein.

NOVEL SUBSTITUTED INDOLO 4,3 FG QUINOLINES USEFUL FOR TREATING MIGRAINE

Provided herein are novel ergoline derivatives and pharmaceutical 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-HTand or 5-HTreceptor 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 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein. 21. The method of claim 1 , wherein the compound of Formula (I) is formulated with a pharmaceutically acceptable vehicle.22. The method of claim 2 , wherein the compound of Formula (II) is formulated with a pharmaceutically acceptable vehicle. This application is a divisional of U.S. patent application Ser. No. 12/978,314, filed on Dec. 23, 2010, which claims priority under 35 U.S.C. §119 (e) from U.S. Provisional Application Ser. No. 61/289,987, filed Dec. 23, 2009, which are hereby incorporated by reference in their entirety.Provided herein are novel ergoline derivatives and pharmaceutical 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-HTand or 5-HTreceptor 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 5-HTreceptor using ...

NOVEL NEUROMODULATORY COMPOUNDS

Provided herein are novel neuromodulatory compounds 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 and Parkinson's disease, using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor 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 alphaand/or the alphareceptors using the compounds and compositions disclosed herein. In other embodiments, provided herein are methods of agonizing dopaminergic Dreceptors and/or antagonizing or inhibiting activity of receptors such as the 5-HTreceptors using the compounds and compositions disclosed herein. 2. The compound of claim 1 , wherein Rand Rare not both —CHCH.3. A composition comprising the compound of and a vehicle.4. A method of treating a migraine in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound of .5. A method of treating a migraine in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the composition of .6. A method of treating one or more symptoms of Parkinson's disease in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound of .7. A method of treating one or more symptoms of Parkinson's disease in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the composition of .8. A method of agonizing the Dreceptor in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound of .9. A method of ...

Platform drug delivery system utilizing crystal engineering and theanine dissolution

A platform drug delivery system and a method of improving the delivery of low solubility pharmaceuticals utilizing crystal engineering and Theanine dissolution resulting in enhanced bioactivity, dissolution rate, and solid state stability.

Novel Cabergoline Derivatives

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-HT 2B receptor and 5-HT 2C receptors the using the compounds and compositions disclosed herein.

PROCESS OF SYNTHESIZING 2-BROMO-LSD

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 [(15)-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 [(15)-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. 1. A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the steps of reacting methylergometrine with N-bromosuccinimide 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 reacting [(1S)-1-(Hydroxymethyl)propylamino][(6aR,9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde with a strong base to yield bromo-lysergic acid as a second intermediate, wherein bromo-lysergic acid is then reacted with an acylating agent in the presence of an amine to yield 2-bromo-LSD or a salt or hydrate thereof. The present application claims the benefit of the filing date of U.S. Provisional Patent Application 62/101,278, filed Jan. 8, 2015, the disclosure of which is hereby incorporated by reference herein in its entirety.The synthesis of BOL-148 in the United States and many other countries is plagued with a handful of regulatory and chemistry issues. The first synthesis of 2-Bromo-LSD (BOL-148) comprised reacting 13.2 grams of N-bromosuccinimide (in 400 mL dioxane) with 1.2 liters of dioxane containing 25 grams of LSD. This gave 11 grams of crude product, which had to be recrystallized. The radioactive synthesis uses effectively elemental bromine, and provided yields ranging from 5 to 15%.LSD is a ...

ISOERGOLINE COMPOUNDS AND USES THEREOF

Provided herein are isoergoline compounds and pharmaceutical 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 pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT, 5-HTand 5-HTreceptors without agonizing the 5-HTreceptor using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HTadrenergic alphaand/or the alphareceptors 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. 124-. (canceled)26. The compound of claim 25 , wherein Ris methyl.27. The compound of claim 26 , wherein Rand R claim 26 , together with the atoms to which they are joined form a double bond.28. The compound of claim 27 , wherein Ris hydrogen claim 27 , CF claim 27 , Br claim 27 , or cyclopropyl.29. The compound of claim 28 , wherein Ris hydrogen.30. The compound of claim 28 , wherein Ris CF.31. The compound of claim 28 , wherein Ris Br.32. The compound of claim 28 , wherein Ris cyclopropyl.33. The compound of claims 29 , wherein Ris methyl claims 29 , b is 1 claims 29 , and Ris hydrogen.34. The compound of claim 30 , wherein Ris methyl claim 30 , b is 1 claim 30 , and Ris hydrogen.35. The compound of claim 31 , wherein Ris methyl claim 31 , b is 1 claim 31 , and Ris hydrogen.36. The compound of claim 32 , wherein Ris methyl claim 32 , b is 1 claim 32 , and Ris hydrogen.37. The compound of claim 29 , wherein Ris CHCF claim 29 , b is 1 claim 29 , and Ris hydrogen.38. The compound of claims 29 , wherein Ris CF claims 29 , b is 1 claims 29 , and Ris hydrogen.39. The compound of ...

POLYCYCLIC COMPOUNDS AND USES THEREOF

The present invention provides novel neuromodulatory compounds and compositions thereof The invention also relates to methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; as well as intermediates for the preparation compounds. 2. The method of claim 1 , wherein Ris selected from C-Chaloalkyl.3. The method of claim 2 , wherein Ris CF.4. The method of claim 1 , wherein Ris selected from optionally substituted cyclopropyl.5. The method of claim 1 , wherein n is 0.6. The method of claim 1 , wherein Ris hydrogen.7. The method of claim 1 , wherein Ris unsubstituted C-Calkyl.8. The method of claim 7 , wherein Ris methyl claim 7 , ethyl or propyl.9. The method of claim 8 , wherein Ris ethyl.10. The method of claim 1 , wherein Ris Ccycloalkyl and Ris selected from C-Calkyl substituted with one or more substituents independently selected from halogen claim 1 , —OR claim 1 , —SR claim 1 , —N(R) claim 1 , —NO claim 1 , ═O claim 1 , and —CN.11. The method of claim 1 , wherein when Ris Ccycloalkyl claim 1 , Ris methyl claim 1 , ethyl or propyl claim 1 , each of which is substituted with at least one halogen.12. The method of claim 11 , wherein Ris —CHCF.13. The method of claim 1 , wherein Ris C-Chaloalkyl and Ris —CHCH.14. The method of claim 1 , wherein Ris methyl.16. The method of claim 1 , wherein the heart disease is cardiovascular disease.17. The method of claim 1 , wherein the heart disease is cardiopulmonary disease.18. The method of claim 1 , wherein the heart disease is selected from fibrogenesis or pulmonary arterial hypertension. This application is a continuation of U.S. patent application Ser. No. 15/997,616, filed Jun. 4, 2018, now U.S. Pat. No. _____, which is a continuation application of International Patent Application No. PCT/US2018/035701, filed Jun. 1, 2018, which claims the benefit of U.S. Provisional Patent Application No.62/513,998, filed Jun. 1, 2017 ...

SLOW-RELEASE CONJUGATES OF SN-38

Conjugates of SN-38 that provide optimal drug release rates and minimize the formation of the corresponding glucuronate are described. The conjugates release SN-38 from a polyethylene glycol through a β-elimination mechanism. 2. The conjugate of wherein PEG is a polyethylene glycol of average molecular weight 30 claim 1 ,000 -50 claim 1 ,000 Da.3. The conjugate of wherein q=4.4. The conjugate of wherein R=CN or SONRwherein each Ris alkyl.5. The conjugate of wherein PEG is multi-armed polyethylene glycol of average molecular weight 30 claim 2 ,000-50 claim 2 ,000 Da; X is CH; L is (CH); Ris CN; Y is CONEt; and q=4.6. A pharmaceutical formulation comprising a conjugate of together with a pharmaceutically acceptable excipient.7. The formulation of claim 6 , wherein the pH of the formulation is between 4.0 and 6.0.9. A method of providing continuous claim 1 , low-dose exposure to SN-38 to a patient in need of such exposure claim 1 , said method comprising administering to the patient the conjugate of .10. The method of claim 9 , wherein the concentration of free SN-38 is maintained between 15 and 5 nM between once-weekly administrations.11. The method of wherein the C/Cobserved between administrations is less than or equal to 10 between once-weekly administrations.12. The method of wherein the C/Cobserved between administrations is less than or equal to 5 between once-weekly administrations.13. A method to control the level of SN-38 glucuronide (SN-38G) in the plasma of a patient requiring treatment with SN-38 claim 1 , said method comprising administering the conjugate of to said patient claim 1 , wherein the resulting SN-38G/SN-38 ratio is less than 0.2. This application is a continuation of U.S. application Ser. No. 15/026,579, having an international filing date of 3 Oct. 2014, which is the national phase of PCT application PCT/US2014/059146 having an international filing date of 3 Oct. 2014, which claims benefit of U.S. Provisional Application Ser. No. 61/887,111 ...

ERGOLINE DERIVATIVES AS DOPAMINE RECEPTOR MODULATORS

The invention provides compounds of formula (I) wherein R-Rhave any of the values defined in the specification, and salts thereof. The compounds are useful as dopamine receptor modulators for the treatment of diseases where modulation of dopamine receptors is implicated (e.g. sexual dysfunction, prolactinoma, Parkinson's disease, and Cushings disease). 3. The compound of wherein Ris —C(═O)NRR.4. The compound of wherein Ris —C(═O)OR.5. The compound of wherein Ris (C-C)alkyl claim 1 , (C-C)alkanoyl claim 1 , (C-C)alkoxycarbonyl claim 1 , or (C-C)alkanoyloxy claim 1 , wherein any (C-C)alkyl claim 1 , (C-C)alkanoyl claim 1 , (C-C)alkoxycarbonyl claim 1 , or (C-C)alkanoyloxy can optionally be substituted with one or more halo claim 1 , hydroxy claim 1 , (C-C)alkoxy claim 1 , (C-C)alkanoyl claim 1 , (C-C)alkoxycarbonyl claim 1 , (C-C)alkanoyloxy claim 1 , or NRR.6. The compound of wherein Ris (C-C)alkyl claim 1 , optionally substituted with one or more (C-C)alkoxy.7. The compound of wherein Ris dimethoxymethyl.8. The compound of wherein Ris N-(3-dimethylaminopropyl)aminocarbonyl.11. The compound of wherein Ris H.12. The compound of wherein Ris (C-C)alkyl.13. The compound of wherein Ris methyl.14. A pharmaceutical composition comprising a compound as described in and a pharmaceutically acceptable diluent or carrier.15. A method for treating sexual dysfunction claim 1 , prolactinoma claim 1 , Parkinson's disease claim 1 , depression claim 1 , restless leg syndrome claim 1 , or Cushings disease in an animal comprising administering a compound of formula I or a pharmaceutically acceptable salt thereof as described in to the animal.1618-. (canceled)19. A method for modulating the activity of a dopamine receptor in an animal comprising administering a compound of formula I or a pharmaceutically acceptable salt thereof as described in to the animal.2021-. (canceled) This application claims priority to U.S. Provisional Application No. 61/728,121 that was filed on Nov. 19, 2012. ...

Composition and Method for Treating Metabolic Disorders

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects. 1. Bromocriptine citrate.2. A pharmaceutical dosage form comprising bromocriptine citrate.3. A pharmaceutical dosage form comprising bromocriptine citrate and pharmaceutically acceptable excipients.4. The pharmaceutical dosage form of comprising an oral dosage form.5. The pharmaceutical dosage form of further comprising a low moisture content filler claim 2 , a water-scavenging agent or a lubricant.6. The pharmaceutical dosage form of further comprising at least one excipient that affects the rate of bromocriptine citrate release from said dosage form.7. The pharmaceutical dosage form of further comprising a disintegrating agent.8. The pharmaceutical dosage form of further comprising at least one of cornstarch claim 2 , mannitol claim 2 , colloidal silicon dioxide or stearic acid.9. The pharmaceutical dosage form of comprising between about 0.05 μg and about 0.5 mg/kg of body weight of bromocriptine citrate.10. The pharmaceutical dosage form of further comprising citric acid.11. The pharmaceutical dosage form of further comprising ...

PROCESS OF SYNTHESIZING 2-BROMO-LSD

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. 1. A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the steps of reacting methylergometrine with N-bromosuccinimide 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 , and then reacting [(1S)-1-(Hydroxymethyl)propylamino][(6aR ,9R)-5-bromo-7-methyl-4 ,7-diaza-4 ,6 ,6a ,7 ,8 ,9-hexahydroacephenanthrylen-9-yl]formaldehyde with a strong base to yield bromo-lysergic acid , wherein bromo-lysergic acid is then reacted with an acylating agent in the presence of an amine to yield 2-bromo-LSD or a salt or hydrate thereof.2. The method of claim 1 , wherein the amine is diethylamine.3. The method of claim 1 , wherein the amine is dimethylamine.4. The method of claim 1 , wherein bromo-lysergic acid is reacted with POCland diethylamine.5. The method of claim 4 , wherein a ratio of an amount of POClto an amount of bromo-lysergic acid ranges from about 1:1 to about 1:3.6. The method of claim 1 , wherein the strong base is KOH.7. A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the step of reacting bromo-lysergic acid with POCl claim 1 , wherein a ratio of an amount of POClto an amount of bromo-lysergic acid ranges from about 1:1 to about 1:3. The present application claims the benefit of the filing date of U.S. Provisional Patent ...

Method for preparing ergolin derivatives

The novel ergoline derivatives of the general formula I …<CHEM>… wherein R1 represents an ally or alkoxy group having from 1 to 4 carbon atoms, phenyl, a 5- or 6-membered heterocyclic ring which is preferably saturated, an amino group, a substituted amino group of the formula NHR min (wherein R min represents an alkyl group having from 1 to 4 carbona toms, a cycloalkyl group, a benzyl group or a phenyl group), or a substituted amino group of the formula NR sec R''' (wherein R sec and R''' both represent alkyl groups having from 1 to 4 carbon atoms);… R2 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms or a phenyl group;… R3 represents a halogen atom, a cyano group, a halogenated lower alkyl group, methylthio, methylsulfonyl or sulfonamido group, an alkoxy group having from 1 to 4 carbon atoms, an acyl group, having from 2 to 5 carbon atoms or a benzoyl group;… R4 represents a hydrocarbon group having from 1 to 4 carbon atoms;… R<5> represents a hydrogen atom or a methoxy group;… R6 is hydrogen, a halogen atom or a methyl group;… R7 is hydrogen or a methyl group;… and the pharmaceutically acceptable addition salts with organic or inorganic acids thereof exhibit antihypertensive and antiprolactinic activity. Their preparation is described, e.g. 2-cyano3- (6 min -methyl-ergoline-8 min beta )-propionic acid ethyl ester is obtained by reacting sodium ethyl cyanoacetate with 6-methyl-8 beta -tosyloxymethylergoline.

METHOD FOR PRODUCING ERGOLIN DERIVATIVES

Способ получени производных /эрголинил/-N,N-диэтилмочевины или их солей

麦角灵衍生物的制备方法

本发明提供了一种制备式I的麦角灵衍生物的 方法，该方法是在金属催化剂和磷化合物存在下使式 II的麦角灵酰胺与式III的异氰酸酯反应，式I的化合 物是有用的抗促乳素和抗帕金森氏病的药物。

Method of obtaining d-2-halogen-6-methyl-8-cyanomethyl- or d-2-halogen-6-methyl-8-carboxamidomethylergolines

Method of preparing 6-methyl-8-substituted-methylergolines or their salts

Method of preparing d-2-substituted-6-methyl-8-cyanomethyl-8-cyanomethylergolines or salts thereof

Method of producing ergolines or physiologically acceptable salts thereof

A process for preparing an ergoline of the formula wherein C s = C 10 is a CC single or double bond, R' is a hydrogen or CONR 2 , R being hydrogen, methyl, or ethyl, and wherein NR' is in the a- or β-position, R 2 is lower alkyl of up to 3 carbon atoms, and the salts thereof, comprises treating the corresponding ergolinyl carboxylic acid amide with lead (IV) acetate in an aprotic polar solvent; reacting the intermediarily formed corresponding isocyanate with water or with a reactive amine of up to 4 carbon atoms, (e.g. a mono- or dialkylamine of up to 4-C atoms); and, optionally, treating the resultant product with an acid to form the corresponding salt.

Method for producing lysergic acid amides or their salts

Patent JPS5813541B2

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The method of obtaining derivatives of ergolene or ergolin

Isoergoline compounds and uses thereof

METHOD FOR PRODUCING LYSERGINIC ACID

1. Способ получения лизергиновой кислоты, включающий изомеризацию паспаловой кислоты в смеси с разделенными фазами, содержащей паспаловую кислоту и водный раствор гидроксида металла.2. Способ по п.1, где гидроксид металла выбран из гидроксида натрия и гидроксида калия.3. Способ по п.2где смесь с разделенными фазами содержит по меньшей мере около 5% по массе паспаловой кислоты.4. Способ по п.3, где водный раствор гидроксида натрия или гидроксида калия содержит по меньшей мере около 12% по массе гидроксида натрия или гидроксида калия, растворенного в воде.5. Способ по п.3, где изомеризацию осуществляют при температуре в пределах около 40-60°C.6. Способ по п.2, дополнительно включающий подкисление реакционной смеси после изомеризации для образования кристаллической соли лизергиновой кислоты.7. Способ по п.6, где реакционную смесь подкисляют до значения pH около 4 или меньше.8. Способ по п.6, где для подкисления реакционной смеси используют серную кислоту.9. Способ по п.6, дополнительно включающий выделение соли лизергиновой кислоты.10. Способ по п.9, дополнительно включающий экстракцию лизергиновой кислоты из выделенной соли лизергиновой кислоты смесью спирта и водного раствора аммиака с образованием раствора лизергиновой кислоты.11. Способ по п.10, где спиртом является метанол.12. Способ по п.11, дополнительно включающий уменьшение объема раствора лизергиновой кислоты.13. Способ по п.12, дополнительно включающий кристаллизацию лизергиновой кислоты из уменьшенного в объеме раствора лизергиновой кислоты.14. Способ по п.13, где кристаллизацию ускоряют добавлением воды.15. Способ по п.13, дополнительно включающий выделение кристаллической А 2006133547 Ко РОССИЙСКАЯ ФЕДЕРАЦИЯ 19 11) мае см хх а (13 9 ВИ“ 2006 133 547 А (51) МПК С070 457/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21), (22) Заявка: 2006133547/04, 17.02.2005 (71) Заявитель(и): ИВАКС ФАРМАСЬЮТИКАЛЗ с.р.о. (С2) (30) Конвенционный ...

Method of producing 2-halogen-nicergolines

The invention relates to a novel process for the preparation of partially new 2-halonicergoline derivatives of the formula (I), <IMAGE> (I) wherein X stands for chlorine, bromine or iodine atom, as well as their acid addition salts. The process of the invention comprises esterifying a novel 2-halo-1-methyllumilysergol of the formula (II), <IMAGE> (II) wherein X is the same as defined above, or an acid addition salt thereof and, if desired, converting the thus-obtained 2-halonicergoline derivative of the formula (I) to an acid addition salt. The compounds of the invention improve the cognitive function of the brain and show an antihypoxic as well as a strong alpha -adrenerg blocking and calcium-antagonistic action.

Slow-release conjugates of sn-38

최적의 약물 방출 속도를 제공하고 대응하는 글루커로네이트 형성을 최소화하는 SN-38의 컨쥬게이트가 개시된다. 상기 컨쥬게이트는 베타-제거 메커니즘을 통하여 폴리에틸렌 글라이콜로부터 SN-38을 방출한다. Conjugates of SN-38 are disclosed that provide an optimal rate of drug release and minimize the corresponding glucuronate formation. The conjugate releases SN-38 from polyethylene glycol via a beta-elimination mechanism.

Method of preparing d-2,6-dimethyl-8-cianmethylergoline or salts thereof

Process for the preparation of cabergoline

Method of producing derivatives of 8,8-disubstituted 6-methylergolines or their salts

Process for producing dihydrolisergol

Использование: е качестве промежуточного продукта в синтезе лекарств Сущность изобретени : продукт дигидролизергол, выход 93,9 - 98,5%, т.пл. 288&amp;deg;С (разл ). Реагент 1 лизергол Реагент 2 водород над палла- диевым катализатором на угле услови  реакции , в смеси N, N-диметилформамида и пиридина, при температуре от 40&amp;deg; до 80&amp;deg;С и давлении от 1 до 5 бар.

Process for preparing derivatives of 2-brom-alpha-ergo-cryptine

LYSURIDE, TERGURIDE AND THEIR DERIVATIVES FOR APPLICATION IN PREVENTION AND / OR TREATMENT OF FIBROUS CHANGES

1. Лизурид или тергурид или производное общей формулы (I):R: алкил, алкинилR: этил, n-пропил, i-пропил, алкилR: водород, метил, этил, n-пропил, i-пропил, -CHOHпричем связь между С/Спредставляет собой или одинарную связь или двойную связь,для применения в профилактике и/или лечении фиброзных изменений органов и их сосудистой структуры в организме человека или животного для остановки и/или для регенерации указанных фиброзных изменений органов и их сосудистой структуры.2. Лизурид или тергурид или производное общей формулы (I) для применения в профилактике и/или лечении по п.1 для продления жизни живого организма.3. Лизурид или тергурид или производное общей формулы (I) для применения в профилактике и/или лечении по п.1 или 2, причем в течение времени лечения по меньшей мере 80% времени, предпочтительно по меньшей мере 100% времени лечения, распределение 5-HT- и/или 5-HT-рецептора в органе-мишени составляет по меньшей мере 90%.4. Лизурид или тергурид или производное общей формулы (I) для применения в профилактике и/или лечении по п.3, причем в течение общего времени лечения распределение 5-HT- и/или 5-HT-рецептора в органе-мишени является полным.5. Лизурид или тергурид или производное общей формулы (I) для применения в профилактике и/или лечении по пп.1, 2 и 4, причем уровень действующего вещества в системной циркуляции живого существа в течение времени лечения составляет по меньшей мере 80% времени, предпочтительно 100% времени непрерывно по меньшей мере 5 пг/мл, более предпочтительно по меньшей мере 100 пг/мл, более предпочтительно по меньшей мере 200 пг/мл, в большинстве случаев предпочтительно 300-500 пг/мл.6. Лизурид или тергурид или производное общей формулы (I) РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2013 126 522 A (51) МПК A61K 9/19 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2013126522/15, 04.11.2011 (71) Заявитель(и): ЗИНОКСА ФАРМА УГ (DE) Приоритет(ы): (30) Конвенционный приоритет: 11.11.2010 DE ...

Nitrogenated aromatic heterocyclic derivative, and organic electroluminescent element using same

헤테로 원자를 가져도 좋은 인데노카바졸 골격, 또는 헤테로 원자를 가져도 좋은 인데노인돌 골격 중의 질소 원자가, 다이벤조퓨란 또는 다이벤조싸이오펜과 직접적 또는 간접적으로 연결되어 있는 질소 함유 방향족 복소환 유도체, 및 그것을 이용한 유기 EL 소자에 의해, 발광 효율이 높고, 장수명인 유기 EL 소자를 실현하는 유기 EL 재료를 제공한다. A nitrogen-containing aromatic heterocyclic derivative in which the nitrogen atom in the indenocarbazole skeleton, which may have a hetero atom, or the indenoindole skeleton, which may have a hetero atom, is directly or indirectly linked to dibenzofuran or dibenzothiophene, And an organic EL material using the same, which realizes an organic EL device having high luminous efficiency and long life.

Method of producing n-alkylated dihydrolysergic acid

The present invention provides a process for preparing wherein R' is C 3 -C e alkyl, -CH 2 C 2 -C 4 alkenyl, propargyl, C 3 -C 8 cycloalkyl or C 1 -C 6 alkyl substituted C 3 -C 8 cycloalkyl; which comprises: reacting a compound of Formula (II): with a substituted benzenesulfonate of Formula III): wherein R' is as defined above and R 2 is hydrogen, bromo, methyl or nitro, in the presence of a base.

Process for preparing derivatives of ergol-8-ene or ergoline or their salts

The invention relates to new ergol-8-ene and ergoline derivatives of the general formula /I/ <IMAGE> /I/ wherein x y stands for -CH=C= or -CH2-CH= group, R stands for hydrogen atom or methyl group, R1 stands for hydrogen or halogen atom, R2 stands for lower alkylsulfonyloxy group, phenylsulfonyloxy group optionally substituted with a lower alkyl group, or azido group, R3 stands for lower alkylsulfonyloxy group or phenylsulfonyloxy group optionally substituted with a lower alkyl group, and acid addition salts thereof. These compounds can be prepared from compounds of the general formula II <IMAGE> /II/ wherein x y and R are as defined above, by reacting at least two equivalents of a lower alkylsulfonic acid chloride or phenylsulfonic acid chloride substituted with lower alkyl group. The resulting compound can be reacted with an alkali metal azide, and, if desired, the compound obtained is treated with a halogenating agent to form the 2-halogenide derivative, and, if desired, any resulting compound of general formula I is treated with an acid to form a therapeutically acceptable acid addition salt, or the free base is liberated from a salt. The compounds of general formula I possess valuable antiserotonine, antidepressant, dopamine receptor stimulant and hypotensive effects.

Method of extraction of alkaloids of ergot from cultural suspensions

Cycioalkyliamides of (8beta)-1-alkyl-6-(substituted) ergolines

本发明提供(8β)-N-环烷基-1-烷基-6-(取代的)麦角灵-8-甲酰胺类化合物和以这类化合物作为活性成份的组合物，以及它们的制备法。这类化合物和含有这类化合物的组合物可以用于阻断哺乳动物5HT受体。这些哺乳动物的中枢或外周有过量的5-羟色胶。本发明还提供用本发明化合物治疗性机能障码、高血压、偏头痛、血管痉挛、血栓形成、局部缺血、抑郁、焦虑、睡眠障碍、食欲障碍的方法。

Method of obtaining 8-thiomethyl-ergolines or salts thereof

Method of preparing lysergol derivatives

A novel process is disclosed for the preparation of derivatives of lysergol having the general formula: According to this process lysergol is directly used as the starting compound and, after the methylation at the 1 position of the corresponding 10 alpha-methoxy-lumilysergol, the methylated compound is directly esterified with a carboxylic acid R-COOH, the acid being selected in the group comprisig aliphatic, cycloatiphatic, aromatic, and heterocyclic carboxylic acids, containing up to 10 carbon atoms.

METHOD OF OBTAINING PEPTIDE-CONTAINING ERGOALKALOIDS

Method of producing 2-bromine derivatives of ergoalkaloids

Method for production of derivative of ergoline

FIELD: organic technology; pharmacology. SUBSTANCE: derivative of ergoline having formula I wherein R 1 -C 2 H 5 ,R 2 -(CH 2 ) 3 N(CH 3 ) 2 ,, R 3 is allyl, R 4 =R 5 =H is prepared by interaction of ergoline amide having formula II with 1-4 equivalents of isocyanate having formula III . In formulae II and III R 1 ,R 2 ,R 3 ,R 4 and R 5 are as mentioned above; interaction is carried out in 1,1-dichloroethane or in toluene at 35-60 C in the presence of CuCl and in the presence of phosphorous compound chosen of PPh 3 ,P(pClPh) 3 ,P(pMePh) 3 and MePh 2 P. Compounds having formula I are suitable as antiprolactinic and antiparcinsonic agents. EFFECT: improved efficiency of the method. ссср с ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ” 2 118 323 Сл 51) М с 070 457/06, А 61 К 31/48 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 93058546/04, 15.02.1993 (30) Приоритет: 12.03.1992 СВ 9205439.4 (46) Дата публикации: 27.08.1998 (56) Ссылки: СВ, 2074566 А, С 070 457/06, 1981. СВ, 2103603 А, С ОГО 457/06, 1983. (71) Заявитель: Фармация энд Апджон, С.П.А. (Т) (72) Изобретатель: Илариа Кандиани (1Т), Уолтер Кабри (1Т), Анжело Бедески (!Т), Франко (54) СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНОГО ЭРГОЛИНА (57) Реферат: Изобретение относится к улучшенному способу получения производного эрголита формулы |, где К. - С>Нё, К> - (СН). М (СН 3)2, Кз - аллил, Ка — К5 — Н, взаимодействием амида эрголита формулы 1 с 1 -4 эквивалентами изоцианата формулы Ш, где К, К К, № и КВ имеют вышеуказанные значения, в 1,1-дихлорэтане или толуоле, при {бот 35°С до 60°С в присутствии СичС! и соединения фосфора, выбранного из РРАз, Р(рОРП)5, Р(рМеРп)з и МеРп->Р. Соединения | являются полезными в качестве антипролактиновых и антипаркинсоновых агентов. м Зарини (1Т) (73) Патентообладатель: < Фармация энд Апджон С.П.А. (1Т) о © сч © со == ТТ, == Сс' > 0 ТТТ Способ выполняется при более мягких условиях, с меньшим избытком изоционата, а продукт | получают с более высокой ...

Method of producing tert-butyl-derivative of ergoline

Ergoline derivatives of general formula I <CHEM> wherein either R1 represents a hydrogen atom or a methoxy group and R2 represents a hydrogen atom or R1 and R2 taken together represent a chemical bond, and R3 represents a hydrogen atom, an unsubstituted or substituted nicotinoyl group or a 1-oxo-2-cyclopenten-3-yl group; or a pharmaceutically acceptable salt thereof are active at the Central Nervous System level and useful therefore in the treatment of cerebral insufficiency and senile dementia.

Compounds and methods to inhibit or augment an inflammatory response

Process for preparing ergolin derivatives

Ergoline derivatives of formula (I) …<CHEM>… wherein R1 represents a hydrogen atom or a methyl group, R2 represents a hydrogen atom or a methoxy group, X represents an oxygen or sulphur atom or a NH or NCH3 group, R3 represents a hydrogen atom, a trifluoromethyl or phenyl group or an alkyl group having from 1 to 4 carbon atoms, R4 represents a hydrogen atom, a methyl or acetyl group or an alkyl group having from 1 to 4 carbon atoms, or R3 and R4 together represent a 3 or 4 membered carbon atom chain, Y represents an electron withdrawing group such as a cyano, nitro, alkylsulphonyl or alkylsulphinyl group or a group of the formula COR5 wherein R5 represents an alkyl group having from 1 to 4 carbon atoms or a phenyl, alkoxy, amino or N-substituted amino group or R5 an R3 together represent a 2 or 3 membered carbon atom chain, R6 represents a hydrocarbon group having from 1 to 4 carbon atoms or a benzyl or phenethyl group, and R7 represents a hydrogen or halogen atom or a methyl or formyl group or a group of the formula SR8 wherein R8 represents an alkyl group having from 1 to 4 carbon atoms or a phenyl group. The pharmaceutically acceptable addition salts and their preparation are disclosed. In form of therapeutical compositions the compounds exhibit useful pharmacological properties.

Improved preparation method of nicergoline

本发明涉及一种尼麦角林的改进制备方法，该方法包括以下步骤：(1)在适量浓硫酸催化和紫外光照射条件下，使麦角醇与甲醇进行光反应，制得10α‑甲氧基光麦角醇；(2)在酰胺类非质子溶剂中，加入无机碱，使10α‑甲氧基光麦角醇与碘甲烷进行甲基化反应生成1‑甲基‑10α‑甲氧基光麦角醇；(3)在溶剂中，以有机胺为缚酸剂，将5‑溴烟酸与草酰氯反应制得5‑溴烟酰氯中间体，再将5‑溴烟酰氯中间体与1‑甲基‑10α‑甲氧基光麦角醇进行缩合反应，制得尼麦角林。与现有技术相比，本发明反应无需惰性气体保护、酸用量小、反应副产物易回收利用，产品最终产率能达到50％以上，产品纯度99％以上，适合规模化生产。

Method of preparing ergoline derivatives

New ergoline derivatives are disclosed which are compounds of formula (I) having the structure: <IMAGE> (I) wherein R1 is hydrogen or methoxy; R2 is hydrogen or methyl; and X is hydroxy, R3COO, S-R4 or NR5R6 in which R3 is a straight or branched alkyl having from 1 to 6 carbon atoms, unsubstituted- or substituted-phenyl, the substituents being selected from the class consisting of chlorine, bromine, alkyl or alkoxy having from 1 to 4 carbon atoms, cycloalkyl containing from 3 to 6 carbon atoms, or a heterocycle; R4 is phenyl or a heterocycle, and R5 and R6 are alkyl having from 1 to 4 carbon atoms, or together with the N atom to which they are attached, forming a heterocycle. The heterocycle may be a 5- or 6-membered ring which contains from 1 to 3 hetero atoms selected from the class consisting of nitrogen, oxygen and sulphur, and may be saturated or unsaturated, and unsubstituted or substituted by halogen, alkyl having from 1 to 3 carbon atoms, hydroxy, nitro, amino, CONHNH2 and COOH.

Process for preparing derivatives of ergoi-8-ene or ergoline or their salts

The invention relates to new ergol-8-ene and ergoline derivatives of the general formula /I/ <IMAGE> /I/ wherein x y stands for -CH=C= or -CH2-CH= group, R stands for hydrogen atom or methyl group, R1 stands for hydrogen or halogen atom, R2 stands for lower alkylsulfonyloxy group, phenylsulfonyloxy group optionally substituted with a lower alkyl group, or azido group, R3 stands for lower alkylsulfonyloxy group or phenylsulfonyloxy group optionally substituted with a lower alkyl group, and acid addition salts thereof. These compounds can be prepared from compounds of the general formula II <IMAGE> /II/ wherein x y and R are as defined above, by reacting at least two equivalents of a lower alkylsulfonic acid chloride or phenylsulfonic acid chloride substituted with lower alkyl group. The resulting compound can be reacted with an alkali metal azide, and, if desired, the compound obtained is treated with a halogenating agent to form the 2-halogenide derivative, and, if desired, any resulting compound of general formula I is treated with an acid to form a therapeutically acceptable acid addition salt, or the free base is liberated from a salt. The compounds of general formula I possess valuable antiserotonine, antidepressant, dopamine receptor stimulant and hypotensive effects.

Substituted indolo 4,3 FG quinolines useful for treating migraine

Provided herein are substituted indolo[4,3-fg]quinolines of Formula (I) and (II) where R 1 -R 6 and R 13 are as defined in the specification and pharmaceutical compositions thereof which are useful in treating, preventing, or ameliorating a variety of medical disorders such as, for example, migraine. In other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT 1D and or 5-HT 1B 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 5-HT 2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein.

Novel fluoroergoline analogs

本发明提供了新型氟麦角碱衍生物和其组合物。在其它实施方案中，本发明提供了使用本发明公开的化合物和组合物治疗、预防或改善多种医学病症诸如，例如偏头痛的方法。在另一些其它实施方案中，本发明提供了使用本发明公开的化合物和组合物激动受体诸如，例如5-HTiD和／或5-HT1B，而不激动5-HT2B受体的方法。在另一些其它实施方案中，本发明提供了使用本发明公开的化合物和组合物拮抗或抑制受体诸如，例如肾上腺素能α2A和／或α2B受体的活性的方法。

Novel iso-ergoline derivatives

Provided herein are novel iso-ergoline 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-HT

Novel neuromodulatory compounds

Provided herein are novel neuromodulatory compounds 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 and Parkinson's disease, using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT

Cabergoline derivatives

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-HT 2B receptor and 5-HT 2C receptors the using the compounds and compositions disclosed herein.

Novel methysergide derivatives

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.

Ergoline compounds and uses thereof

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-HT 1A , 5-HT 1B and 5-HT 1D receptors without agonizing the 5-HT 2B receptor using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HT 2B adrenergic alpha 2A and/or the alpha 2B 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.

Isoergoline compounds and uses thereof

Provided herein are isoergoline compounds and pharmaceutical 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 pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT

Ergoline derivatives for use in medicine

The present invention provides novel neuromodulatory compounds and compositions thereof. The invention also relates to methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; as well as intermediates for the preparation compounds.

Novel preparation method of nicergoline

本发明涉及一种尼麦角林的新制备方法，该方法包括以下步骤：(1)在极性非质子溶剂中，加入无机碱，使麦角醇(II)与甲基化试剂进行甲基化反应，生成1‑甲基麦角醇(III)；(2)1‑甲基麦角醇(III)与甲醇在浓硫酸的催化下进行光反应，制得1‑甲基‑10α‑甲氧基光麦角醇(IV)；(3)在极性非质子有机溶剂中，以N,N’‑羰基二咪唑为缩合剂，将5‑溴烟酸(V)与N,N’‑羰基二咪唑先反应制得5‑溴烟酰咪唑(VI)中间体，再将5‑溴烟酰咪唑(VI)中间体与1‑甲基‑10α‑甲氧基光麦角醇(IV)进行缩合反应，制得尼麦角林(I)。与现有技术相比，本发明无需惰性气体保护、酸用量小、产品质量好、收率高、反应副产物易回收利用，适合工业化生产。

Method of preparing ergolin-8-ylalkylethers, thioethers and prostanic acid amides

<P>L'invention concerne de nouvelles prostaglandines et leur préparation. </P><P>Les composés de l'invention répondent à la formule :</P> The invention relates to novel prostaglandins and their preparation. </ P> <P> The compounds of the invention have the formula: </ P>

CRYSTALLINE SODIUM SALT OF PARECOXIB

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (51) ÌÏÊ 7 (11) 2004 127 585 (13) A C 07 D 261/08, A 61 K 31/42, A 61 P 29/00 ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2004127585/04, 12.03.2003 (71) Çà âèòåëü(è): ÔÀÐÌÀÖÈß ÊÎÐÏÎÐÅÉØÍ (US) (30) Ïðèîðèòåò: 15.03.2002 US 60/364,567 11.10.2002 US 60/417,987 (43) Äàòà ïóáëèêàöèè çà âêè: 10.04.2005 Áþë. ¹ 10 (87) Ïóáëèêàöè PCT: WO 03/07840 (25.09.2003) Àäðåñ äë ïåðåïèñêè: 129010, Ìîñêâà, óë. Á.Ñïàññêà , 25, ñòð.3, ÎÎÎ "Þðèäè÷åñêà ôèðìà Ãîðîäèññêèé è Ïàðòíåðû", ïàò.ïîâ. Ã.Á. Åãîðîâîé R U Ôîðìóëà èçîáðåòåíè 1. Íàòðèåâà ñîëü ïàðåêîêñèáà â êðèñòàëëè÷åñêîé ôîðìå, êîòîðà âë åòñ ïî ñóùåñòâó áåçâîäíîé è ïî ñóùåñòâó íåñîëüâàòèðîâàííîé. 2. Íàòðèåâà ñîëü ïàðåêîêñèáà ïî ï.1, êîòîðà âë åòñ ôîðìîé À, îòëè÷àþùà ñ , ïî ìåíüøåé ìåðå, êàðòèíîé ïîðîøêîâîé ðåíòãåíîãðàììû, èìåþùåé ïî ìåíüøåé ìåðå äâå âåëè÷èíû 2θ, âûáðàííûå èç ãðóïïû, ñîñòî ùåé èç âåëè÷èí 5,6, 9,6, 11,0 è 14,5±0,2 ãðàäóñà. 3. Íàòðèåâà ñîëü ïàðåêîêñèáà ïî ï.1, êîòîðà âë åòñ ôîðìîé À, îòëè÷àþùà ñ , ïî ìåíüøåé ìåðå, êàðòèíîé ïîðîøêîâîé ðåíòãåíîãðàììû, ïî ñóùåñòâó ñîîòâåòñòâóþùåé ôèã.1. 4. Íàòðèåâà ñîëü ïàðåêîêñèáà ïî ï.1, êîòîðà âë åòñ ôîðìîé À, îòëè÷àþùà ñ , ïî ìåíüøåé ìåðå, èíôðàêðàñíûì ñïåêòðîì ñ ïðåîáðàçîâàíèåì Ôóðüå, ïî ñóùåñòâó ñîîòâåòñòâóþùèì ôèã.2. 5. Íàòðèåâà ñîëü ïàðåêîêñèáà ïî ï.1, êîòîðà âë åòñ ôîðìîé À, îòëè÷àþùà ñ , ïî ìåíüøåé ìåðå, òåðìîãðàììîé äèôôåðåíöèàëüíîé ñêàíèðóþùåé êàëîðèìåòðèè, ïî ñóùåñòâó ñîîòâåòñòâóþùåé ôèã.3. 6. Íàòðèåâà ñîëü ïàðåêîêñèáà ïî ï.1, êîòîðà âë åòñ ôîðìîé Â, îòëè÷àþùà ñ , ïî ìåíüøåé ìåðå, êàðòèíîé ïîðîøêîâîé ðåíòãåíîãðàììû, èìåþùåé ïî ìåíüøåé ìåðå äâå âåëè÷èíû 2θ, âûáðàííûå èç ãðóïïû, ñîñòî ùåé èç âåëè÷èí 4,2, 8,3, 12,4, 16,7, 17,5, 20,8 è 24,7±0,2 ãðàäóñà. 7. Íàòðèåâà ñîëü ïàðåêîêñèáà ïî ï.1, êîòîðà âë åòñ ôîðìîé Â, îòëè÷àþùà ñ , ïî ìåíüøåé ìåðå, êàðòèíîé ïîðîøêîâîé ðåíòãåíîãðàììû, ïî ñóùåñòâó ñîîòâåòñòâóþùåé ôèã.5. Ñòðàíèöà: 1 RU A 2 0 0 4 1 2 7 5 8 5 A (54) ÊÐÈÑÒÀËËÈ×ÅÑÊÀß ...

Method of producing 2-halogenated 1,8-substituted derivatives of ergolene

The invention relates to novel 2-halogenated 8- and 1,8-substituted ergolene derivatives of the formula (I) and the acid addition salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the formula (I) <IMAGE> (I) wherein X stands for a halogen; R stands for a C1-4 alkyl group and R'' means a hydroxyl group; or R stands for an acyl or substituted acyl group and R'' represents a halogen or an -OR' group, wherein R' stands for an acyl or substituted acyl group; or R stands for hydrogen and R'' means a halogen or an -OR' group, wherein R' stands for an acyl or substituted acyl group; and the dotted line means a double bond between the 8-9 or 9-10 positions. The compounds of the formula (I) possess an antipsychotic and antihypoxic action and a negligable extrapyramidal side-effect.

Process for producing derivatives of 6-methyl-8-beta-hydrazinomethylergolin or their salts

The invention relates to new 8 beta -hydrazinomethyl-ergoline derivatives of the general formula (I), <IMAGE> (I) wherein x y stands for a <IMAGE> or <IMAGE> group, R stands for hydrogen or methyl group, and R1 stands for hydrogen, a lower acyl group, a di-(lower-alkylaminocarbonyl group, a group of the general formula (VI), <IMAGE> (VI) wherein Z1, Z2 and Z3 each represent hydrogen, halogen or a trifluoromethyl group, or a group of the general formula (VII), <IMAGE> (VII) wherein Y represents a lower alkyl group, allyl group or phenyl group, and acid addition salts thereof. These compounds possess valuable antiserotonine, antidepressant and hypotensive effects, furthermore they can be applied as starting substances in the preparation of other biologically active ergoline derivatives. The new compounds of the general formula (I) are prepared according to the invention by reacting the respective 6-methyl-8 beta -mesyloxymethyl or -tosyloxymethyl-ergoline derivatives with dry hydrazine. In order to obtain the N-substituted hydrazinomethyl compounds, the N-unsubstituted derivatives are reacted with an acylating agent or with an isothiocyanate.

The method of obtaining derivatives of 9,10-dihydro-lysergic acid

Method of obtaining 2-brom-alpha-ergocryptine or acid-additive salts thereof

The invention relates to a novel process for the halogenation in 2-position of ergot alkaloids. The process is characterized by that as a halogenating agent a system consisting of dimethylsulfoxide, a trialkylhalosilane or triarylhalosilane and optionally a hydrogen halide is used.

Method of obtaining derivatives of 8-(bis-aminoethyl)-ergoline-1 and their salts

Process for the preparation of ergoline derivatives

본 발명은 일반식(Ⅱ)의 에르골린 아미드를 금속촉매 및 인 화합물의 존재하에 일반식(Ⅲ)의 이소시아네이트와 반응시킴을 포함하여, 일반식(I)의 에르골린 유도체를 제조하는 방법에 관한 것이다. The present invention relates to a method for preparing an ergoline derivative of formula (I), comprising reacting an ergoline amide of formula (II) with an isocyanate of formula (III) in the presence of a metal catalyst and a phosphorus compound will be. 일반식(I)의 화합물은 유용한 항프롤락틴제 및 파킨슨병 치료제이다. Compounds of formula (I) are useful antiprolactin agents and therapeutic agents for Parkinson's disease.

1-Alkyl-ergolinyl-thiourea derivative, process for producing the same and drug having central α-lower 2 receptor-blocking action containing the same

Ergoline derivatives for use in medicine

本发明提供了新型神经调节化合物及其组合物。本发明还涉及使用本发明化合物治疗各种疾病、病症和病况的方法；制备本发明化合物的方法；以及用于制备化合物的中间体。

Method of preparing lysergic acid amides or salts thereof

Process for preparing ergoline derivatives or their salts

A description is given of the preparation of ergolene derivatives with an action lowering blood pressure and the formula I <IMAGE> in which R1 and R2 are each hydrogen or an alkyl group with 1 to 4 carbon atoms, or else together form an alkylidene chain with a maximum of 5 carbon atoms, and their salts with acids. Corresponding compounds unsaturated in position 2,3 are reduced selectively in position 2,3 and the resulting compounds of the formula I are converted where appropriate into their acid addition salts.

Method of producing derivatives of pyrazolo[3,4]quinoline or pyrido[2,3]quinazoline, or their salts

7- or 8-Substituted, partially hydrogenated pyrazolo[3,4-g]quinoline, thiazolo[4,5-g]quinoline, oxazolo[4,5-g]quinoline, and pyrrolo[3,4-g]quinoline derivatives, and 8- or 9-substituted, partially hydrogenated pyrido[2,3-g]quinazoline derivatives of formula: <CHEM> wherein: <CHEM> represents <CHEM> <CHEM> <CHEM> <CHEM> <CHEM> or <CHEM> are D-2 dopamine agonists. 6-Oxo-1-substituted-octahydroquinolines and 6-oxo-1-substituted-decahydroquinolines which are additionally substituted in the 3- or 4-position are intermediates useful in preparation of the dopamine agonists. Acetals of 4,6-dioxo-1-substituted-decahydroquinoline 3-carboxylic acid esters enable synthesis of the foregoing compounds.

Method of obtaining 6-methyl-8beta-(substituted)-methylergolines or their salts

Method of producing ergoline derivative

Изобретение касаетс  производных эрголина, в частности получени  10-метокси-1,6-диметил-8β-(1-C 1 -C 4 -алкил-1,4-дигидро-3-пиридилкарбонилоксиметил)-эрголинов, которые обладают активностью в отношении центральной нервной системы и могут быть использованы дл  лечени  метаболических сосудистых церебральных нарушений. Цель - создание новых активных веществ указанного класса. Их синтез ведут восстановлением четвертичной галоидной соли эрголина с помощью дитионита натри  в слабоосновном водном растворе при 5-25°С. Новые соединени  малотоксичны (LD 50 *98800 мг/кг) и могут быть использованы по указанному назначению. 1 табл.

Process for the preparation of bcd tricychic ergoline paristructure analogues

내용 없음.

Method of obtaining n-b-substituted derivatives of 8-(b-aminoethyl) ergolin-1 or their salts

Process for preparing crystalline form of cabergoline

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.

8,8-Disubstituted-6-methylergolines and related compounds

8,8-Disubstituted-6-methylergolines and 9-ergolenes, prepared by alkylation of lysergic, isolysergic or their 9,10-dihydro analogues, optionally followed by chemical modification of an 8-substituent.

ERGOLINE DERIVATIVES, PROCESS FOR PREPARING THEM AND THEIR USE AS MEDICAMENTS

DERIVES DE L'ERGOLINE, PROCEDE POUR LES PREPARER ET LEUR EMPLOI COMME MEDICAMENTS. CES COMPOSES REPONDENT A LA FORMULE I: (CF DESSIN DANS BOPI) DANS LAQUELLE R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE METHYLE, R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE METHOXY, X REPRESENTE UN ATOME D'OXYGENE OU DE SOUFRE OU UN GROUPE NH OU NCH, R REPRESENTE UN ATOME D'HYDROGENE, UN GROUPE TRIFLUOROMETHYLE OU PHENYLE OU UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE, R REPRESENTE UN ATOME D'HYDROGENE, UN GROUPE METHYLE OU ACETYLE, UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE, OU R ET R REPRESENTENT ENSEMBLE UNE CHAINE PRESENTANT 3 OU 4 ATOMES DE CARBONE, Y REPRESENTE UN GROUPE DE RETRAIT D'ELECTRON TEL QU'UN GROUPE CYANO, NITRO, ALKYSULFONYLE OU ALKYLSULFINYLE OU UN GROUPE DE FORMULE COR DANS LAQUELLE R REPRESENTE UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE OU UN GROUPEPHENYLE, ALCOXY, AMINO OU AMINO N-SUBSTITUE, OU R ET R REPRESENTENT ENSEMBLE UNE CHAINE PRESENTANT 2 OU 3 ATOMES DE CARBONE, R REPRESENTE UN GROUPE D'HYDROCARBURE AYANT DE 1 A 4 ATOMES DE CARBONE OU UN GROUPE BENZYLE OU PHENETHYLE, R REPRESENTE UN ATOME D'HYDROGENE OU D'HALOGENE OU UN GROUPE METHYLE OU FORMYLE OU UN GROUPE DE FORMULE SR DANS LAQUELLE R REPRESENTE UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE OU UN GROUPE PHENYLE. LEUR PREPARATION SE FAIT PAR CONDENSATION DANS L'HEXAMETHYLPHOSPHOTRIAMIDE D'UN INTERMEDIAIRE APPROPRIE DE FORMULE II: (CF DESSIN DANS BOPI) DANS LAQUELLE R, R, R ET R ONT LA SIGNIFICATION DONNEE DANS LA REVENDICATION 1, AVEC UN SEL ALCALIN D'UN COMPOSE DE FORMULE III: (CF DESSIN DANS BOPI) DANS LAQUELLE R, R, X ET Y ONT LA SIGNIFICATION INDIQUEE DANS LA REVENDICATION 1, APRES QUOI, SI ON LE DESIRE, ON AJOUTE UN ACIDE ORGANIQUE OU INORGANIQUE POUR OBTENIR UN SEL D'ADDITION. ERGOLINE DERIVATIVES, PROCESS FOR PREPARING THEM AND THEIR USE AS MEDICINAL PRODUCTS. THESE COMPOUNDS MEET FORMULA I: (CF DRAWING IN ...

Patent FR2297628B1

Patent FR2252098A1

PROCESS FOR THE PREPARATION OF N-METHYL DERIVATIVES OF METHYL DIHYDROLYSERGATE OR METHYL METHOXYLUMILYSERGATE

Patent FR2293204B1

N- (8A-ERGOLINYL) -N ', N'-DIETHYLUREES, 1-SUBSTITUTED AND PROCESS FOR OBTAINING THESE COMPOUNDS

A.L'INVENTION CONCERNE DES PRODUITS CHIMIQUES NOUVEAUX PRESENTANT UNE ACTIVITE PHARMACEUTIQUE. B.CES PRODUITS SONT CONSTITUES PAR LES N-(8A-ERGOLINYL)-N,N-DIETHYLUREES SUBSTITUEES EN 1, DE FORMULE GENERALE I: (CF DESSIN DANS BOPI) DANS LAQUELLE R REPRESENTE UN GROUPE ALCOYLE AVEC 1 A 4 ATOMES DE CARBONE ET R REPRESENTE UN GROUPE ALCOYLE INFERIEUR AVEC 1 A 4 ATOMES DE CARBONE, UN GROUPE BENZYLE, UN GROUPE ALLYLE OU UN GROUPE DE FORMULE GENERALE-(CH)COOR, OU R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE ALCOYLE AVEC 1 A 2 ATOMES DE CARBONE, ET N EST UN NOMBRE ENTIER DE 1 A 4. C.CES PRODUITS PRESENTENT DES PROPRIETES INTERESSANTES COMME INHIBITEURS DE LA SECRETION DE PROLACTINE ET DE L'HORMONE DE CROISSANCE ET COMME STIMULATEURS DE LA SECRETION DE GONADOTROPINES CHEZ L'ANIMAL. A. THE INVENTION RELATES TO NEW CHEMICALS SHOWING PHARMACEUTICAL ACTIVITY. B. THESE PRODUCTS CONSTITUTE THE N- (8A-ERGOLINYL) -N, N-DIETHYLUREES SUBSTITUTED IN 1, OF GENERAL FORMULA I: (CF DRAWING IN BOPI) IN WHICH R REPRESENTS AN ALCOHYL GROUP WITH 1 TO 4 CARBON ATOMS AND R REPRESENTS A LOWER ALCOYL GROUP WITH 1 TO 4 CARBON ATOMS, A BENZYL GROUP, AN ALLYL GROUP OR A GROUP OF GENERAL FORMULA- (CH) COOR, OR R REPRESENTS A HYDROGEN ATOM OR AN ALCOYL GROUP WITH 1 TO 2 CARBON ATOMS, AND N IS A WHOLE NUMBER FROM 1 TO 4. C. THESE PRODUCTS SHOW INTERESTING PROPERTIES AS INHIBITORS OF PROLACTIN AND GROWTH HORMONE SECRETION AND AS STIMULATORS OF GONADOTROPIN SECRETION IN ANIMALS.

New derivatives of 6-methyl- and 1,6-dimethyl-ergoline i.

Process for the preparation of n- / d-6-methyl-8-isoergolényl / -n ', n'-diethyl-urea

New derivatives of the lysergic acid series and their preparation

PROCESS FOR BROMINATING ALKALOIDS IN RYE ERGOT AND COMPOUNDS OBTAINED

L'INVENTION CONCERNE UN PROCEDE DE PREPARATION DES ALCALOIDES DE L'ERGOT DE SEIGLE DE FORMULE: (CF DESSIN DANS BOPI) DANS LAQUELLE R REPRESENTE UN GROUPE CARBOXY, ALCOXY-CARBONYLE, CARBAMOYLE EVENTUELLEMENT SUBSTITUE, OU UN GROUPE CARBAMOYLE SUBSTITUE PAR UN RESTE PEPTIDIQUE APPARTENANT AUX ALCALOIDES DE L'ERGOT DE SEIGLE. SELON LE PROCEDE DE L'INVENTION, ON BROME UN COMPOSE CORRESPONDANT DE FORMULE: (CF DESSIN DANS BOPI) PAR REACTION AVEC UN COMPLEXE DE BROME DE LA 3-BROMO-6-CHLORO-2-METHYL-IMIDAZO1,2-BPYRIDAZINE. CE PROCEDE PERMET DE BROMER SELECTIVEMENT LES ALCALOIDES DE L'ERGOT DE SEIGLE. THE INVENTION CONCERNS A PROCESS FOR THE PREPARATION OF ALKALOIDS FROM RYE ERGOT OF FORMULA: (CF DRAWING IN BOPI) IN WHICH R REPRESENTS A CARBOXY, ALCOXY-CARBONYL, CARBAMOYL, POSSIBLY SUBSTITUTED, OR A SMALL CARBAMOYL GROUP. BELONGING TO THE ALKALOIDS OF ERGOT OF RYE. ACCORDING TO THE PROCESS OF THE INVENTION, A CORRESPONDING COMPOUND OF FORMULA: (CF DRAWING IN BOPI) IS BROMINATED BY REACTION WITH A 3-BROMO-6-CHLORO-2-METHYL-IMIDAZO1,2-BPYRIDAZINE BROMINE COMPLEX. THIS PROCESS ALLOWS SELECTIVELY BROMING THE ALKALOIDS OF RYE ERGOT.

2,3-DIHYDROERGOLINS

(6)-methyl-(8)-pyridyl-thiomethyl-ergoline and (9)-ergolene - antidepressants and central dopaminergic receptor stimulants used to treat Parkinson's disease opt. with a phosphodiesterase inhibitor

Lysergic acids derivs. of formula (I) and their acid addn. salts are novel cpds. (where R is 3-pyridyl, x y is -CH=C and the -CH2SR gp. has beta configuration or R is 2-pyridyl, x y is -CH=C or -CH2-CH and the -CH2SR gp. has alpha-configuration). Cpds. (I) are administered orally rectally or parenterally in daily doses of 1-100mg taken as one or several unit doses. The central dopaminergis stimulatory activity is potentialised by phosphodiesterase inhibitors such as theophylline, caffeine, 4-amino-1H-pyrazolo(3,4-b)pyridine-5-carboxylic acid derivs, 4-(3,4-dimethoxybenzyl)-2-imidazolidinone and analogous derivs and minor tranquillisers such as benzodiazepines and dibenzazepines (I) may be administered, with the phosphodiesterase inhibitor, in daily doses of 0.5-50mg; the ratio (I):phosphodiesterase inhibitor being 1:10 to 1:50. The three cpds. which may be prepd. by the methods of the parent patent comprise 6-methyl-8 beta-(3-pyridylthiometyl)DELTA 9-ergolene, 6-methyl-5 alpha-(2-pyridylthiomethyl)-ergoline and 6-methyl-8 alpha-(2-pyridylthiomethyl)-DELTA 9-ergolene.

Patent FR2000364A1