3489results about "Carbamic acid derivatives preparation" patented technology

This invention concerns multiple release spacers and spacer systems, which release multiple leaving groups following a single activation. It concerns compounds comprising a specifier linked to two or more of the same or different leaving groups (L in the figure) via a self-eliminating multiple release spacer or spacer system, which compounds upon a single activation step, in particular removal or transformation of the specifier, release at least two leaving groups.

The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

A 4-membered compound is represented by the following formula (I) is disclosed (in the formula, X1 and X2 each independently represent an oxygen atom, a sulfur atom or a substituted or unsubstituted imino group, Y1 and Y2 each independently represent a single bond, an oxygen atom or a substituted or unsubstituted imino group, B1 and B2 each independently represent an optionally substituted aliphatic, aliphatic carbonyl, aromatic or aromatic carbonyl group having 1-20 carbon atoms, and A1 and A2 each independently represent a group represented by the following formula (II) (Ar1, Ar2 and Ar3 each independently represent a cyclic group having 5-14 carbon atoms, L1 and L2 each independently represent a single bond or a divalent linking group, and p represents an integer of 0-2)). There is also disclosed a birefringence medium containing a 4-membered compound represented by the formula (I) and an optical element comprising the birefringence medium.

(A1) Translate this text The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure (I) wherein R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(0)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ?-aminoalkyl, ?-(substituted)aminoalky, ?-phosphoalkyl or ?-thiophosphoalkyl.

The invention provides substituted diaryl compounds as shown in general formula (I) or their pharmaceutically acceptable salts, and also provides a preparation method; a class of novel broad-spectrum antiviral compounds and pharmaceutical salts targeting cytokines are screened and obtained through studies on structure-activity relationship and action mechanism of active compounds; the compounds not only have significant broad-spectrum antiviral activity, but also have the advantages of low toxicity and good pharmaceutical properties.

The present invention relates to a synthetic process for the preparation of a novel class of androgen receptor targeting agents (ARTA) which demonstrate androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. The agents define a new subclass of compounds which are selective androgen receptor modulators (SARM) which are useful for a) male contraception; b) treatment of a variety of hormone-related conditions, for example conditions associated with Androgen Decline in Aging Male (ADAM), such as fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, anemia, obesity, sarcopenia, osteopenia, osteoporosis, benign prostate hyperplasia, alterations in mood and cognition and prostate cancer; c) treatment of conditions associated with Androgen Decline in Female (ADIF), such as sexual dysfunction, decreased sexual libido, hypogonadism, sarcopenia, osteopenia, osteoporosis, alterations in cognition and mood, depression, anemia, hair loss, obesity, endometriosis, breast cancer, uterine cancer and ovarian cancer; d) treatment and / or prevention of chronic muscular wasting; e) decreasing the incidence of, halting or causing a regression of prostate cancer; f) oral androgen relacement and / or other clinical therpauetic and / or diagnostic areas. The process of the present invention is suitable for large-scale preparation, since all of the steps give rise to highly pure compounds, thus avoiding complicated purification procedures which ultimately lower the yield. Thus the present invention provides methods for the synthesis of non-steroidal agonist compounds, that can be used for industrial large-scale synthesis, and that provide highly pure products in high yield.

The present invention provides a method for synthesizing 1-(acyloxy)-alkyl derivatives from 1-acyl-alkyl derivatives, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and / or toxic compounds and is readily amenable to scale-up. The current invention also provides 1-acyl-alkyl derivatives of known drug compounds and methods for synthesizing these 1-acyl-alkyl derivatives.

Disclosed is a method for synthesizing 1-(acyloxy)-alkyl derivatives of primary or secondary amine drugs from 1-acyl-alkyl derivatives of primary or secondary amine drugs, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and / or toxic compounds and is readily amenable to scale-up. For example, 1-acyl-alkyl derivatives of gabapentin and pregabalin are oxidized to yield 1-(acyloxy)-alkyl derivatives of gabapentin and pregabalin, respectively.

The present invention provides compounds that block calcium channels and have the Formula I:The present invention also provides pharmaceutical compositions containing the compounds of Formula I and methods of using them to treat stroke, cerebral ischemia, head trauma, and epilepsy.

The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

This invention is directed to compounds of the following formula:wherein when a is 0, b is 1 or 2; when a is 1, b is 1, m is from 0-3, X is 0 or S, Y is halogeno, R1 is hydrogen C1-4 alkyl, R2 is hydrogen, C1-4 alkyl, or optionally substituted propargyl and R1 and R4 are each independently hydrogen, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl each optionally substituted.This invention is also directed to the use of these compounds for treating depression, Attention Deficit Disorder (ADD), Attention Deficit and Hyperactivity Disorder (ADHD), Tourette's Syndrome. Alzheimer's Disease and other dementia's such as senile dementia, dementia of the Parkinson's type, vascular dementia and Lewy body dementia.This invention is further directed to a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

Conjugates in which polyamine analogs are conjugated to an amino acid are provided, as well as compositions comprising these conjugates. Methods of using these conjugates as anticancer treatments are also provided.

The disclosure relates to di-aliphatic substituted PEGylated lipids and to methods of their preparation. The disclosure also relates to lipid conjugates containing di-aliphatic substituted PEGylated lipids, and to the use of di-aliphatic substituted PEGylated-lipid conjugates in drug delivery.

Compounds and methods of selectively inhibiting an immunoproteasome are described. Also described are methods of treating a cancer, an inflammation, and / or an autoimmune disease and methods of suppressing endogenous antigenic peptide generation by administering to a subject in need of treatment thereof a therapeutic amount of an immunoproteasome specific inhibitor.

Disclosed herein are methods for synthesizing 1-(acyloxy)-alkyl prodrug derivatives of drugs through oxidation of 1-acyl-alkyl derivatives of drugs under anhydrous reaction conditions. The methods typically proceed stereospecifically, in high yield, do not require the use of activated intermediates and / or toxic compounds and are readily amenable to scale-up.

A mutant hydrolase optionally fused to a protein of interest is provided. The mutant hydrolase is capable of forming a bond with a substrate for the corresponding nonmutant (wild-type) hydrolase which is more stable than the bond formed between the wild-type hydrolase and the substrate. Substrates for hydrolases comprising one or more functional groups are also provided, as well as methods of using the mutant hydrolase and the substrates of the invention. Also provided is a fusion protein capable of forming a stable bond with a substrate and cells which express the fusion protein.

Disclosed is a process for isolating from a reaction mixture a salt of a mono-propargylated aminoindan having the structure wherein R1 is H, hydroxyl, alkoxy or wherein Y is O or S; R2 and R3 is each, independently, C1-8 alkyl, C6-12 aryl, C6-12 aralkyl, each optionally halo substituted, or hydrogen; where the reaction mixture further comprises a solvent, a primary aminoindan having the structure wherein R1 is defined as above, and a tertiary aminoindan having the structure the process comprising d) adding an acid to the reaction mixture; e) crystallizing the mono-propargylated aminoindan under conditions suitable for the formation of a crystalline salt of the mono-propargylated aminoindan; and f) recovering the crystalline salt of the mono-propargylated aminoindan, wherein the process is performed without addition of an organic solvent. Also disclosed are the crystalline diastereomeric salts produced by the process and pharmaceutical compositions containing the salts.

Compounds of Formula 1, Formula 2 or Formula 3 where X is O, S, or (CR1R1)n where n is 0, 1 or 2; Y is a bivalent radical having Formula 4 or Formula 5 where o is an integer from 1 to 4 or Y is a bivalent aryl or 5 or 6 membered heteroaryl radical having 1 to 3 heteroatoms selected from N, S and O, said aryl or heteroaryl groups being unsubstituted, or substituted with 1 to 3 C1-6 alkyl or with 1 to 3 C1-6 fluoroalkyl groups; and the remaining symbols have the meaning described in the specification, have RXR selective retinoid agonist-like activity.

This invention pertains to novel methods for the synthesis of certain nitrogen mustard prodrugs, such as N-{4-[N,N-bis(2-haloethylamino)-phenoxycarbonyl}-L-glutamic acid: wherein: X2 is a halo group, and is —F, —Cl, —Br, or —I; n is an integer from 0 to 4; and, each RA is an aryl substituent. The methods comprise, at least, the steps of: glutamate conjugation (GC); silyloxy deprotection (SD); and, sulfonic esterification (SU). Certain preferred methods comprise the steps of: amine substitution (AS); silyloxy protection (SP); phenolic deprotection (PD); activation (AC); glutamate conjugation (GC); silyloxy deprotection (SD); sulfonic estenfication (SU); halogenation (HL); glutamate deprotection (GD); and glutamic acid protection (GP).

The present invention relates to carboxamide compounds of general formula I wherein the groups and residues A, B, W, X, Y, Z, R<1>, R<2>, R<3 >and k have the meanings given in claim 1. Moreover the invention relates to process for preparing the above mentioned carboxamides as well as pharmaceutical compositions containing at least one carboxamide according to the invention. In view of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and / or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.

The present invention provides for a rheology control agent that includes a following compound represented by the following formula: wherein A, B, C and D equal CH2, CHR, NH, or O, and A, B, C and D may be the same or different and at least one of A and B equals NH and at least one of C and D equals NH; and wherein R1, R2, and R3 may be the same or different and represent a linear, branched, hyper-branched, or dendritic ether, polyether or hydrocarbon based chain, optionally forming at least one carbon-based ring, being saturated or unsaturated and R2 represents linear or branched alkylenes, ethers, polyethers, or polyester linkages and at least one of R1, R2, and R3 comprises an ester group or an amide group which is branched off from the main chain; excluded from Formula (1) is a compound wherein R2 is CH2—CH2—CH2—CH2—CH(C(O)OCH3), A, B, C, and D are equal to NH and R1 and R3 are both equal to a linear octyl hydrocarbon chain; the rheology control agent is suitable for solvent-borne and water-borne coating composition having improved rheology control useful for OEM refinishing or repainting the exterior of automobile and truck bodies and parts thereof.

A reagent for oligonucleotide synthesis or purification, wherein the reagent has a structure of:X—C-L-H  (Formula A)wherein X is a phosphoramidite group, an H-phosphonate group, an acetal group, or an isocyanate; C is a direct bond or a cleavable adaptor represented by —Ca-Cb—; L is a hydrocarbyl chain; and H is a terminal alkyne or an activated cyclooctyne. The reagent of Formula (A) can be used in the synthesis and purification of oligonucleotides.

1-phenyl-3-dimethylaminopropane compounds corresponding to the formula I a method of preparing them, and the use of these substances as analgesic active ingredients in pharmaceutical compositions.

Compounds of formula (I): wherein: R1 is alkyl; R2a, R2b, R2c and R2d are the same or different and each is hydrogen, optionally substituted alkyl or various other organic groups; R3 is alkyl; R4 is a group of formula (II), (III), (IV), (V), (VI), (VII), (VIII) or (IX): wherein: A1 is a single bond, alkylene or alkenylene; A2 is or alkenylene; A3 is a single bond, alkyleneor alkenylene; R5a and R5b are the same or different and each is hydrogen, alkyl or various other groups; R6 is alkyl or phenyl; R7 is hydrogen or alkyl; R8 is alkyl or various other groups; and n is 0 and pharmaceutically acceptable salts thereof have valuable inhibitory activity against acyl-CoA: cholesterol acyl transferase.

The present invention provides novel dimeric cationic lipids. The present invention further provides compositions of these lipids with anionic or polyanionic macromolecules, methods for interfering with protein expression in a cell utilizing these compositions and a kit for preparing the same.

The invention is directed to a method of treating addiction to drugs of abuse in a subject, comprising administering a therapeutically effective amount of a cabamoyl compound, or pharmaceutically acceptable salt or ester thereof.

The present invention relates to copper-catalyzed carbon-heteroatom and carbon-carbon bond-forming methods. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of an amide or amine moiety and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In additional embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between a nitrogen atom of an acyl hydrazine and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In other embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of a nitrogen-containing heteroaromatic, e.g., indole, pyrazole, and indazole, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-oxygen bond between the oxygen atom of an alcohol and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. The present invention also relates to copper-catalyzed methods of forming a carbon-carbon bond between a reactant comprising a nucleophilic carbon atom, e.g., an enolate or malonate anion, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. Importantly, all the methods of the present invention are relatively inexpensive to practice due to the low cost of the copper comprised by the catalysts.

A process for isolating from a reaction mixture a salt of a mono-propargylated aminoindan, a process for isolating from a reaction mixture a crystalline diastereomeric salt of a mono-propargylated aminoindan, and a process for isolating from a reaction mixture a salt of enantiomerically pure N-propargyl-1-aminoindan or a salt of enantiomerically pure 6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan. The corresponding products are also disclosed.