32 results about "Cannabinoid Receptor Modulators" patented technology

Pharmaceutical compositions in which isolated cannabinoid receptor modulators are optionally combined with terpene blends in a pharmaceutically acceptable carrier. Methods for treating or preventing a disease, disorder, dysfunction or condition caused by exposure to an organophosphate or carbamate acetylcholineesterase inhibitor with the inventive compositions are also disclosed.

A cannabinoid receptor modulator containing a compound represented by Formula (I0) wherein, X is an oxygen atom, etc., R0 is an optionally substituted acylamino group, ring A0 is a benzene ring which may further have a substituent in addition to R0, and ring B is an optionally substituted 5-membered heterocycle, or a salt thereof or a prodrug thereof.

The present disclosure provides Diels-Alder adducts of chalcone and prenylphenyl moieties capable of modulating the activity of cannabinoid receptors, and to oligomers of flavan-3-ol capable of modulating fat absorption and storage. Such Diels-Alder adducts of chalcone and prenylphenyl moieties or oligomers of flavan-3-ol can optionally be used in combination with other weight management agents, such as anorectic agents, a lipase inhibitors, other cannabinoid receptor modulators, psychotropic agents, insulin sensitizers, stimulants, or satiety agents, as well as to methods of use thereof such as treating or preventing weight gain or obesity, promoting weight loss, appetite suppression, modifying satiety, or the like.

Novel compounds of structural formula (I) are antagonists and / or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as psychotropic drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinsons disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as, the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

A cannabinoid receptor modulator which contains a compound represented by the formula (I0): (I0) (wherein X represents oxygen, etc.; R0 represents optionally substituted acylamino; ring A0 represents a benzene ring optionally having a substituent besides R0; and ring B represents optionally substituted five-membered heterocycle), a salt of the compound, or a prodrug of either.

Compounds of formula (I) are modulators of cannabinoid receptor CB1, useful inter alia for treatment of obesity: Formula (I). Wherein: X is a bond, or a divalent radical selected from —C(R10)(R11)—*, —C(R10)(R11)—O—*, —C(R10)(R11)CH2—*, —C(R10)(R11)CH2—O—*, —CH2C(R10)(R11)—*, —CH2C(R10)(R11)—O—*. and —CH2—O—C(R10)(R11)—*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; Z is a carboxyl isostere radical selected from the group specified; R3 is hydrogen, (C1-C)alkyl or (C1C3)fluoroalkyl; R4 is a radical of formula -(Alk1)p-(Q1)r (L)s-Q2 wherein p, r, s, Alk1, L, Q1 and Q2 are as specified; or R3and R4 taken together with the nitrogen to which they are attached form a cyclic amino ring of 4 to 7 ring atoms which is optionally substituted by a radical of formula -(L)s-Q2 wherein s, L and Q2 are as defined above, or by an optional substituent selected from hydroxy, methoxy, —NH2—, or mono- or di-(C1C3)alkylamino; R5, R6, R7 and R8 are each independently selected from hydrogen —F, —Cl, —Br, —CN, (C1-C3)alkyl, (C1C3)fluoroalkyl, cyclopropyl, and —OR9; R10 is hydrogen, (C1C3)alkyl, hydroxyl or NH2, and R11 is hydrogen or (C1-C3)alkyl; or R10 and R11 taken together with the carbon atom to which they are attached form a (C3-C5)cycloalkyl ring.

The present disclosure provides Diels-Alder adducts of chalcone and prenylphenyl moieties capable of modulating the activity of cannabinoid receptors, and to oligomers of flavan-3-ol capable of modulating fat absorption and storage. Such Diels-Alder adducts of chalcone and prenylphenyl moieties or oligomers of flavan-3-ol can optionally be used in combination with other weight management agents, such as anorectic agents, a lipase inhibitors, other cannabinoid receptor modulators, psychotropic agents, insulin sensitizers, stimulants, or satiety agents, as well as to methods of use thereof such as treating or preventing weight gain or obesity, promoting weight loss, appetite suppression, modifying satiety, or the like.

The invention is directed to the use of at least one CBx modulator wherein the CBx modulator is selected from the group consisting of CB1 agonists; CB2 agonists; CB2 partial agonists; CB2 antagonists; CB2 inverse agonists; and dually acting compounds which are both a CB1 agonist and a CB2 agonist; and mixtures thereof, as KATP channel modulator for the prophylaxis, treatment, delayed progression, delayed onset and / or inhibition of a variety of disease conditions including obesity, diabetes mellitus, metabolic syndrome, syndrome X, insulinoma, familial hyperinsulemic hypoglycemia, male pattern baldness, detrusor hyperreactivity, asthma, neuroprotection, epilepsy, analgesia, cardioprotection, angina, cardioplegia, arrhythmia, coronary spasm, peripheral vascular disease, cerebral vasospasm, appetite regulation, neurodegeneration, pain - including neuropathic pain and chronic pain - and impotence in mammals and humans. The invention further relates to methods of treating, preventing, delaying progression of, delaying onset of and / or inhibiting a variety of disease conditions including obesity, diabetes mellitus, metabolic syndrome, syndrome X, insulinoma, familial hyperinsulemic hypoglycemia, male pattern baldness, detrusor hyperreactivity, asthma, neuroprotection, epilepsy, analgesia, cardioprotection, angina, cardioplegia, arrhythmia, coronary spasm, peripheral vascular disease, cerebral vasospasm, appetite regulation, neurodegeneration, pain - including neuropathic pain and chronic pain - and impotence in mammals and humans comprising administering to a subject in need thereof an effective amount of at least one CBx modulator having KATP channel modulating properties.

The present invention relates to novel cannabinoid receptor modulators, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor modulators, and uses thereof for treating diseases, conditions and / or disorders modulated by a cannabinoid receptor (such as pain, neurodegenative disorders, eating disorders, weight loss or control, and obesity).

The present invention relates to novel cannabinoid receptor modulators, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor modulators, and uses thereof for treating diseases, conditions and / or disorders modulated by a cannabinoid receptor (such as pain, neurodegenative disorders, eating disorders, weight loss or control, and obesity).

Compounds of formula (I), are cannabinoid CB1 receptors, useful, inter alia in the treatment of obesity:wherein A1 is hydrogen, —COOH, or tetrazolyl, and A2 is hydrogen, —COOH, tetrazolyl, —CN, —CF3, —COR6, —SO2R6, —OR7, —NR7R8, —NHCOR6, and —NR7SO2R8 provided that one of A1 and A2 is either —COOH or tetrazolyl; p is 0 or 1 and A3 is phenyl or cycloalkyl, either of which is optionally substituted with R4 and / or R5; q is 0 or 1; R1 is a bond, or —(CH2)aB1(CH2)b— wherein a and b are independently 0, 1, 2 or 3 provided that a+b is not greater than 4, and B1 is —CO—, —O—, —S—, —SO—, —SO2—, —CH2—, —CHOH— or —NR7—; R2 is a bond, —CH2)aB1(CH2)b— or —[(CH2)aB1(CH2)b]n-A4-[(CH2)cB2(CH2)d]m— wherein a, b, and B1 are as defined for R1; B2 is as defined for B1, c and d are independently 0, 1, 2 or 3; with the proviso that a+b+c+d is not greater than 6, n and m are independently 0 or 1 and A4 is a monocarbocyclic or monoheterocyclic ring, having 3 to 8 ring atoms, optionally substituted with one or more of —F, —Cl, —Br, —CN, —CF3, C1-C4 alkyl, cycloalkyl, —OR9, oxo or —NR7R8; R3 is hydrogen, C1-C4 alkyl, cycloalkyl, —CF3, —OR9, —NR7R8, —(CH2)sCOR6, —(CH2)sSO2R6, —(CH2)sNR7COR6, —(CH2)sNR7COOR8, —(CH2)sNR7SO2R6, wherein s is 1, 2, 3 or 4; R4 and R5 independently —R9, —CN, —F, —Cl, —Br, —OR9, —NR7R8, —NR7COR6, —NR7SO2R6, —COR6, —SR9, —SOR9, —SO2R6, (C1-C4 alkyl)OR9, —(C1-C4 alkyl)NR7R8, —(C1-C4 alkyl)NR7COR6, C1-C4 alkyl)NR7COOR8, —(C1-C4 alkyl)NR7SO2R6, —(C1-C4 alkyl)COR6, —(C1-C4 alkyl)SO2R6, —NR7COOR8, or [N—(C1-C4 alkyl)]-tetrazolyl; R6 is C1-C4 alkyl, cycloalkyl, —CF3 or —NR7R8; R7 and R8 are independently hydrogen, C1-C4 alkyl or cycloalkyl; and R9 is hydrogen, C1-C4 alkyl, cycloalkyl, fully or partially fluorinated C1-C4 alkyl.

A compound having the general structure of Formula (I): Chemical formula should be inserted here as it appears on the abstract in paper form. or a pharmaceutically acceptable salt, solvate, or ester thereof, is useful in treating diseases, disorders, or conditions such as obesity, metabolic disorders, addiction, diseases of the central nervous system, cardiovascular disorders, respiratory disorders, and gastrointestinal disorders.

The present invention relates to novel cannabinoid receptor modulators, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor modulators, and uses thereof for treating diseases, conditions and / or disorders modulated by a cannabinoid receptor (such as pain, neurodegenerative disorders, eating disorders, weight loss or control, and obesity).

The present invention relates to novel cannabinoid receptor modulators, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor modulators, and uses thereof for treating diseases, conditions and / or disorders modulated by a cannabinoid receptor (such as pain, neurodegenative disorders, eating disorders, weight loss or control, and obesity).

The invention discloses a nitrogen-containing five-membered heteroaromatic compound as shown in structural formulae (I) and (II), a medicinal derivative, a hydrate, a composition containing the nitrogen-containing five-membered heteroaromatic compound and a preparation method thereof. The invention also disclose an application of the compound as a drug and as a cannabinoid acceptor adjustor for preventing and treating ache, inflammation, immune diseases and central nervous system diseases and the like.

The present invention relates to novel cannabinoid receptor modulators, in particular cannahinoid I (CB1) or cannabinoid 2 (CH2) receptor modulators, and uses thereof for treating diseases, conditions and / or disorders modulated by a cannabinoid receptor (such as pain, neurodegenerative disorders, eating disorders, weight loss or control, and obesity).

The invention relates to the preparation of a curcumin derivative and application of the curcumin derivative as a cannabinoid receptor modulator. In the synthetic route of the curcumin derivative, 10% of Pd-C is used for reducing the curcumin; for protecting a phenolic hydroxyl group, only 2.0% mol of DMAP (Dimethylaminopyridine) is used for catalysis and (Boc)2O of which the mole amount is 2.05 times as much as that of the curcumin is used so that reaction is completely realized; during a Mannich reaction, Mannich reagents such as N,N,N',N'-tetramethyldiaminomethane prepared in advance are used so as to avoid that an acid component reacts with formaldehyde to generate by-products at first. In the whole route, the target compound is obtained through reducing, protection, alkylation, deprotection and the Mannich reaction with the curcumin as the raw material. The route has the characteristics of cheap and available raw material, high yield and easy operation. The curcumin derivative is capable of inhibiting the hepatic stellate cells of a hepatic fibrosis rat from synthesizing and secreting extracellular matrix through a cannabinoid receptor, promoting the degradation of the extracellular matrix, reducing the deposition of the extracellular matrix in the liver and further developing the effect of treating the hepatic fibrosis.

The invention is directed to pharmaceutical compositions comprising pharmacologically effective quantities of each of a) at least one KATP channel modulator as a first active agent and b) at least one CBx modulator as a second active agent. The invention further relates to the use of such compositions and to methods of treating, preventing, delaying progression of, delaying onset of and / or inhibiting a variety of disease conditions including obesity, diabetes mellitus, metabolic syndrome, syndrome X, insulinoma, familial hyperinsulemic hypoglycemia, male pattern baldness, detrusor hyperreactivity, asthma, neuroprotection, epilepsy, analgesia, cardioprotection, angina, cardioplegia, arrhythmia, coronary spasm, peripheral vascular disease, cerebral vasospasm, appetite regulation, neurodegeneration, pain - including neuropathic pain and chronic pain - and impotence in mammals and humans by administering such compositions to subjects in need thereof. The invention also is directed to processes of manufacturing such compositions.

Oral formulations of benzofuran compounds which modulate cannabinoid receptors are presented. Methods of using these formulations for treatment of cannabinoid receptor-mediated disease, including neuropathic pain and addition, are also described.

The present invention relates to particular radiolabeled Cannabinoid-1 (CB1) receptor modulators, and methods of using these modulators for labeling and diagnostic imaging of Cannabinoid-1 receptors in mammals, particularly humans. In addition, intermediates useful for the synthesis of the radiolabeled Cannabinoid-1 receptor modulators are also disclosed, as well as the processes for synthesizing the radiolabeled Cannabinoid-1 receptor modulators. Still further, formulations of the radiolabeled Cannabinoid-1 receptor compounds are described.

Compounds of formula (I) are modulators of cannabinoid receptor CB1, useful inter alia for treatment of obesity: Formula (I). Wherein: X is a bond, or a divalent radical selected from —C(R10)(R11)—*, —C(R10)(R11)—O—*, —C(R10)(R11)CH2—*, —C(R10)(R11)CH2—O—*, —CH2C(R10)(R11)—*, —CH2C(R10)(R11)—O—*, and —CH2—O—C(R10)(R11)—*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; Z is a carboxyl isostere radical selected from the group specified; R3 is hydrogen, (C1-C)alkyl or (C1C3)fluoroalkyl; R4 is a radical of formula -(Alk1)p-(Q1)r (L)s-Q2 wherein p, r, s, Alk1, L, Q1 and Q2 are as specified; or R3and R4 taken together with the nitrogen to which they are attached form a cyclic amino ring of 4 to 7 ring atoms which is optionally substituted by a radical of formula -(L)s-Q2 wherein s, L and Q2 are as defined above, or by an optional substituent selected from hydroxy, methoxy, —NH2—, or mono- or di-(C1C3)alkylamino; R5, R6, R7 and R8 are each independently selected from hydrogen —F, —Cl, —Br, —CN, (C1-C3)alkyl, (C1C3)fluoroalkyl, cyclopropyl, and —OR9; R10 is hydrogen, (C1C3)alkyl, hydroxyl or NH2, and R11 is hydrogen or (C1-C3)alkyl; or R10 and R11 taken together with the carbon atom to which they are attached form a (C3-C5)cycloalkyl ring.

A cannabinoid receptor modulator containing a compound represented by Formula (I0)wherein, X is an oxygen atom, etc., R0 is an optionally substituted acylamino group, ring A0 is a benzene ring which may further have a substituent in addition to R0, and ring B is an optionally substituted 5-membered heterocycle, or a salt thereof or a prodrug thereof.

This invention relates to 4,5-dihydro-(1 H)-pyrazole (pyrazoline) derivatives as cannabinoid CB1 receptor modulators, to pharmaceutical compositions containing these compounds, to methods for their syntheses, methods for preparing novel intermediates useful for their syntheses, and methods for preparing compositions. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in disorders in which CB1 receptors are involved, or that can be treated via manipulation of those receptors. The compounds have formula (I) wherein the symbols have the meanings given in the specification.