Modulation of anxiety through blockade of anandamide hydrolysis

Fatty acid amide hydrolase inhibitors of the Formula: are provided wherein X is NH, CH 2 , O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted biphenylyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted phenyl; substituted or unsubstituted terphenylyl; substituted or unsubstituted cycloalkyl, heteroaryl, or alkyl; and R 1 and R 2 are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and substituted or unsubstituted phenyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; with the proviso that if Z is O, one of R 1 and R 2 is absent, and that if Z is N, optionally R 1 and R 2 may optionally be taken together to form a substituted or unsubstituted N-heterocycle or substituted or unsubstituted heteroaryl with the N atom to which they are each attached. Pharmaceutical compositions comprising the compounds of Formula I and methods of using them to inhibit FAAH and/or treat appetite disorders, glaucoma, pain, insomnia, and neurological and psychological disorders including anxiety disorders, epilepsy, and depression are provided.

Compositions Comprising Enzyme-Cleavable Phenol-Modified Tapentadol Prodrug

A method of providing a patient with controlled release of tapentadol using a prodrug capable, upon enzymatic activation and intramolecular cyclization, of releasing tapentadol is disclosed. The disclosure also provides such prodrug compounds and pharmaceutical compositions comprising such compounds. Such pharmaceutical compositions can optionally include an enzyme inhibitor that interacts with the enzyme(s) to mediate the enzymatically-controlled release of tapentadol from the prodrug so as to modify enzymatic cleavage of the prodrug. Also included are methods to use such compounds and pharmaceutical compositions. 2. The compound of claim 1 , where Ris (1-6C)alkyl.3. (canceled)4. The compound of claim 1 , wherein Ris methyl or ethyl.513-. (canceled)14. The compound of claim 1 , wherein Rand Rare hydrogen.15. The compound of claim 1 , wherein Rand Rwhich are on the same carbon are alkyl.16. (canceled)17. The compound of claim 1 , wherein Rand Rwhich are on the same carbon are methyl.18. The compound of claim 1 , wherein Rand Rwhich are vicinal are both alkyl and Rand Rwhich are vicinal are both hydrogen.1922-. (canceled)23. The compound of claim 1 , wherein one of Rand Ris aminoacyl.2433-. (canceled)34. The compound of claim 1 , wherein n is 2 or 3.35. The compound of claim 1 , wherein Ris a residue of an L-amino acid selected from alanine claim 1 , arginine claim 1 , asparagine claim 1 , aspartic acid claim 1 , cysteine claim 1 , glycine claim 1 , glutamine claim 1 , glutamic acid claim 1 , histidine claim 1 , isoleucine claim 1 , leucine claim 1 , lysine claim 1 , methionine claim 1 , phenylalanine claim 1 , proline claim 1 , serine claim 1 , threonine claim 1 , tryptophan claim 1 , tyrosine and valine claim 1 , or a residue of an N-acyl derivative of any of said amino acids; or a residue of a peptide composed of at least two L-amino acid residues selected independently from alanine claim 1 , arginine claim 1 , asparagine claim 1 , aspartic acid claim 1 , cysteine ...

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

Isocyanates and Aromatic Hydroxy Compounds

An object of the present invention is to provide a process for producing isocyanates, which are industrially useful compounds, without using phosgene, and to provide a process for chemically recycling waste polycarbonate resin. The present invention discloses a process enabling isocyanate compounds to be produced without using phosgene as a raw material by subjecting a carbamic acid ester compound obtained by a reaction between an aromatic polycarbonate resin and an amine compound to a thermal decomposition reaction, while at the same time disclosing a process enabling chemical recycling of aromatic polycarbonate resin by recovering a divalent aromatic hydroxy compound forming aromatic polycarbonates. 119-. (canceled) The present invention relates to a process for producing isocyanate compounds and aromatic hydroxy compounds, which are useful for raw materials for aromatic polycarbonate.Plastics are used as product materials in all fields of daily life, and the amount of plastics used is increasing each year. Accompanying this increase, the amount of discarded plastics is also extremely large, thus resulting in the treatment of plastics becoming a significant social issue.At present, the majority of plastic products are simply disposed of by being incinerated or buried following completion of their use. However, when waste plastic having high heat of combustion in terms of calories is disposed of by incinerating in an ordinary refuse incinerator, abnormal combustion occurs resulting in the problem of damage to the incinerator furnace. In addition, not only does this manner of disposal result in wasted resources, but it also causes environmental problems in terms of environmental contamination and discharge of carbon dioxide gas. Thus, it is extremely important to recycle waste plastics from the viewpoint of the formation of a recycling society as well.Methods used to recycle waste plastics include material recycling, in which waste plastics are reused as is, ...

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1 comprising administering to a subject in need thereof a compound described here. 2. The compound of claim 1 , wherein Ris 3-fluorophenyl.3. The compound of or claim 1 , wherein:{'sup': '1', 'Ris selected from cyclohexyl, cyclopentyl, cycloheptyl, 3,3-difluorocyclobutyl, 4,4,-difluorocyclohexyl, and bicyclo[2.2.1]heptanyl; and'}{'sup': '4', 'Ris selected from 1-(methylmethoxycarbonylamino)ethyl, 1,2,3,4-tetrahydroquinolin-1-yl, 1-ethoxycarbonylpiperidin-2-yl, 1-ethoxycarbonylpyrrolidin-2-yl, 1H-benzimidazol-1-ylmethyl, 1H-indazol-3-ylmethyl, indolin-1-ylmethyl, 1H-indol-3-ylmethyl, 1H-indol-5-ylmethyl, 1H-pyrrolo[2,3-b]pyridine-3-ylmethyl, 1H-pyrrolo[3,2-b]pyridin-3-ylmethyl, 1-methoxycarbonylpiperidin-2-yl, 1-methoxycarbonylpyrrolidin-2-yl, 2-fluoropyridin-3-ylaminomethyl, 2-imino-4-fluoropyridin-1-ylmethyl, 2-methoxyphenylaminomethyl, 2-methyl-1H-benzimidazol-1-ylmethyl, 2-methylimidazol-1-ylmethyl, 2-trifluoromethyl-1H-imidazol-1-yl, 3-cyanophenylaminomethyl, 3-fluoropyridin-2-ylaminomethyl, 3-methoxyphenylaminomethyl, 4-(1,3,4-oxadiazole-2-yl)phenylaminomethyl, 4-(dimethylaminocarbonyloxy)phenylmethyl, 4,5-dichloroimidazol-1-ylmethyl, 4-cyanophenylaminomethyl, 4-fluorophenylaminomethyl, 4-fluoropyridin-2-ylaminomethyl, 4-hydroxyphenylmethyl, 4-methoxycarbonylmorpholin-3-yl, 4-methoxycarbonylpiperazin-1-ylmethyl, 4-methoxyphenylaminomethyl, 4-methylcarbonyloxyphenylmethyl, 5-fluoropyridin-2-aminomethyl, 5-fluoropyridin-2-oxymethyl, 6-fluoropyridin-3-ylaminomethyl, benzomorpholin-4-ylmethyl, methoxycarbonylaminomethyl, methylmethoxycarbonylaminomethyl, methylphenylaminomethyl, phenylaminomethyl, pyridin-2-oxymethyl, pyridin-2-ylaminomethyl, pyridin-2-yloxymethyl, pyridin-3-oxymethyl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, thiazol-4-ylmethyl, and thien-2-ylmethyl.'}4. The compound of claim 1 , wherein the compound is selected from any one of Compound numbers 104 claim ...

PERIPHERALLY RESTRICTED FAAH INHIBITORS

Peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH) are provided. The compounds can suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). Despite their relative inability to access brain and spinal cord, the compounds attenuate behavioral responses indicative of persistent pain in rodent models of inflammation and peripheral nerve injury, and suppresses noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CBi receptor blockade prevents these effects. Accordingly, the invention also provides methods, and pharmaceutical compositions for treating conditions in which the inhibition of peripheral FAAH would be of benefit. The compounds of the invention are according to the formula (I): in which Ris a polar group. In some embodiments, Ris selected from the group consisting of hydroxy and the physiologically hydro lysable esters thereof. Rand Rare independently selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbyl; each Ris independently selected from the group consisting of halogen and substituted or unsubstituted hydrocarbyl and n is an integer from 0 to 4; each Ris independently selected from the group consisting of halo and substituted or unsubstituted hydrocarbyl and m is an integer from 0 to 3; and Ris substituted or unsubstituted cyclohexyl; and the pharmaceutically acceptable salts thereof. 2. The compound of claim 1 , wherein Ris —OC(O)R claim 1 , wherein Ris substituted or unsubstituted hydrocarbyl.3. The compound of claim 1 , wherein Ris O-carboxamido.4. The compound of claim 1 , wherein both of Rand Rare independently selected from (C-C)alkyl and H.5. The compound of claim 1 , wherein Ris unsubstituted cyclohexyl.6. The compound of claim 1 , wherein Rand Rare each independently selected from halogen and substituted or unsubstituted (C-C)alkyl.7. The compound of claim 1 , wherein Ris substituted or unsubstituted ...

PROCESS AND INTERMEDIATES FOR PREPARING MACROLACTAMS

The present invention relates to macrolactam compounds, intermediates useful in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing and modifying macrolactams. One use of the compounds and methods described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. An example of an HCV inhibitory compound that can be synthesized using the procedures described herein is Compound A and derivative thereof. 7. The method of claim 6 , wherein Ris Calkyl and Ris a H or Calkyl.10. The method of claim 9 , wherein said Step C coupling is performed using EDC and pyridine or a pyridine derivative.13. The method of claim 8 , wherein Ris either H or Calkyl.17. The method of claim 13 , wherein Ris either H or Calkyl.19. The method of claim 8 , wherein said ring closure is performed by slow addition of catalyst and the compound of Formula IIa to a solvent at approximately the same time claim 8 , wherein:said solvent is provided at about 5-25 liters per Kg of substrate;said catalyst is provided at a concentration of about 250 ml to 3 L per Kg of catalyst;said compound is provided at a concentration of about 500 ml to 6 L per Kg of substrate; andsaid compound-solution, said catalyst-solution and said solvent are combined together over a period of 0.5-2.5 hrs.2122-. (canceled) The present invention relates to method and compounds that can be used to produce macrolactams, and modify macrolactams. One use of the methods and compounds described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity.Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals. Current treatments for HCV infection include immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin. Several virally-encoded ...

Processes For Preparing A Polymeric Compound

The present invention provides methods for preparing a polymeric compound of Formula I: The present invention was supported, in part, by funds from the U.S. Government (SBIR Phase 1 grant No. 1R43HL090113-01) and the U.S. Government may therefore have certain rights in the invention.The present invention is directed, in part, to methods for preparing a polymeric salicylamide compound and/or pharmaceutically acceptable salts thereof, as well as to useful intermediates for the preparation of the polymeric salicylamide compound and/or pharmaceutically acceptable salts thereof.The polymeric salicylamide compound of Formula I:and/or pharmaceutically acceptable salts thereof are useful, for example, as pharmaceutical agents for inhibiting angiogenesis (see, WO 2005/123660). Given the importance of the compound of Formula I and/or pharmaceutically acceptable salts thereof as pharmaceutical agents, effective synthetic methods for preparing the compound and its pharmaceutically acceptable salts is of great import. This invention is directed to this, as well as other, important ends.The present invention provides, in part, methods for preparing a compound of Formula I:or pharmaceutically acceptable salt thereof, comprising:a) removing the Cbz groups from a compound of Formula II:or pharmaceutically acceptable salt thereof, under a hydrogenation/hydrogenolysis condition to form the compound of Formula I, or pharmaceutically acceptable salt thereof; andb) optionally isolating the compound of Formula I, or pharmaceutically acceptable salt thereof.In some embodiments, the hydrogenation/hydrogenolysis condition comprises using a metal catalyst. In some embodiments, the metal catalyst is Pd/C. In some embodiments, the reaction yield in step a) is greater than about 85%.In some embodiments, the methods further comprise:c) removing the Boc group from a compound of Formula III:or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula II, ...

Process for the manufacture of bridged monobactam intermediates

C1-C6Alkyloxy- or benzyloxy-carbonyl esters of -{3-[(E)-(1-phenyl or naphthyl C1-C4alkyl)-imino]-propyl}-amino)-acetic acid, which are intermediates for producing known bridged monobactam compounds useful in the treatment of bacterial infections.

1H-QUINAZOLINE-2,4-DIONES

The present invention relates to 1H-Quinazoline-2,4-diones of formula (I) 2. Compounds according to claim 1 , wherein{'sup': '1', 'sub': '3', 'Rrepresents CFor iso-Propyl and'}{'sup': '2', 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'Rrepresents (C-C)alkyl substituted by one to three substituents, the substituents being selected from the group consisting of halogen, nitro, cyano, HCO, (C-C)alkylcarbonyl, hydroxy, (C-C)alkoxy, (C-C)alkylcarbonyloxy, (C-C)alkoxycarbonyloxy, amino, (C-C)alkylamino, di(C-C)alkylamino, acylamino, (C-C)alkoxycarbonylamino, except trifluoromethyl or'}{'sup': '2', 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'Rrepresents heterocyclyl(C-C)alkyl substituted by one to three substituents, the substituents being selected from the group consisting of halogen, nitro, cyano, hydroxy, (C-C)alkoxy, (C-C)alkylcarbonyloxy, (C-C)alkoxycarbonyloxy, amino, (C-C)alkylamino, di(C-C)alkylamino, (C-C)alkoxycarbonylamino and the heterocyclyl consist of 3 to 11 ring atoms of which 1-3 ring atoms are hetero atoms or'}{'sup': '2', 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'Rrepresents phenyl substituted by one to three substituents, the substituents being selected from the group consisting of cyano, hydroxy, alkanediyl, alkenediyl, (C-C)alkoxy, (C-C)alkylcarbonyloxy, (C-C)alkoxycarbonyloxy, amino, (C-C)alkylamino, di(C-C)alkylamino, (C-C)alkoxycarbonylamino or'}{'sup': '2', 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'Rrepresents heterocyclyl optionally substituted by one to three substituents, the substituents being selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, (C-C)alkyl, hydroxy(C-C)alkyl, (C-C)alkoxyalkyl, amino(C-C)alkyl, (C-C)alkylamino(C-C)alkyl, di(C-C)alkylamino(C-C)alkyl, HCO, (C-C)alkylcarbonyl, (C-C)alkoxy, acyloxy, (C-C) ...

Method of use of pharmaceutical formulations for the treatment of apicomplexan diseases in animals

The present invention is directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a salicylanilide or salicylanilide derivative, disclosed herein, alone or in combination with one or more other active or excipient pharmaceutical substances. The present invention is further directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a combination of salicylanilides or salicylanilide derivatives, disclosed herein. The present invention is further directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a combination of salicylanilides or salicylanilide derivatives, disclosed herein, further comprised of one or more active or excipient pharmaceutical substances. 1. The method of use of one or more compound of Formula I to prevent or treat a disorder caused wholly or in part by one or more apicomplexan parasite, wherein said method comprises contacting an animal in need of said prevention or treatment with an effective amount said compound, wherein said compound has the structure{'sub': 1', '6, 'R═H, SH, or OR;'}{'sub': 2', '3', '3', '2', '3', '2', '2', '3', '3', '2, 'Rand Rare selected from fused phenyl, H, lower alkyl, I, Br, Cl, F, CF, CHCF, CHPh, CH═CH, C≡CH, OCH, OCF, Ph, OPh, and NO;'}{'sub': 4', '3', '2', '3', '2', '2', '3', '3', '2, 'Ris selected from the group consisting of H, lower alkyl, I, Br, Cl, F, CF, CHCF, CHPh, CH═CH, C≡CH, C≡N, OCH, OCF, Ph, OPh, and NO;'}{'sub': '5', 'Ris H, lower alkyl, or phenyl;'}{'sub': 6', '3', '2', '3', '3', '2', '3', '3', '2', '6', '4', '2', '6', '4', '6', '4', '2', '3', '2', '2', '3', '2', '3', '2', '3', '2', '2', '3', '2, 'Ris selected from the group consisting of H, COCH, COCHCH, COCH(CH), COC(CH), COPh, ...

HYDROQUINONE COMPOUNDS, PREPARATION METHODS THEREFOR, AND USE IN ANTI-TUMOR OR IMMUNOMODULATION THERAPY

Disclosed are hydroquinone compounds, preparation methods therefor, and uses thereof in anti-tumor or immunomodulation. The structural formula of the hydroquinone compounds are shown by formula I, 14-. (canceled)68-. (canceled)91. An anti-tumor drug or immunomodulation drug , comprising an effective amount of a compound as shown in claim , pharmaceutically acceptable salts thereof , hydrates thereof , solvates thereof or a pharmaceutical composition thereof as an active component.10. The anti-tumor drug or immunomodulation drug of claim 9 , wherein the drug releases 2-tert-butyl-4-methyoxyphenyl.141. A process for treating a tumor or for immunomodulation in a subject comprising administering to a subject an effective amount of a compound as shown in claim claim 9 , pharmaceutically acceptable salts thereof claim 9 , hydrates claim 9 , or solvates thereof.15. The process according to claim 14 , wherein the compound releases 2-tert-butyl-4-methoxyphenol.161. A process of controlling 2-tert-butyl-4-methoxyphenol in a subject claim 14 , comprising administering to the subject an effective amount of a compound as shown in claim claim 14 , pharmaceutically acceptable salts thereof claim 14 , hydrates claim 14 , or solvates thereof. The present application is a divisional of U.S. Non-Provisional patent application Ser. No. 16/069,814, entitled “HYDROQUINONE COMPOUNDS, PREPARATION METHODS THEREFOR, AND USE IN ANTI-TUMOR OR IMMUNOMODULATION THERAPY,” and filed on Jul. 12, 2018. U.S. Non-Provisional patent application Ser. No. 16/069,814 is a U.S. National Phase of International Patent Application Serial No. PCT/CN2017/074386, entitled “HYDROQUINONE COMPOUND, PREPARATION METHOD THEREFOR, AND APPLICATION IN TUMOUR RESISTANCE OR IMMUNOMODULATION,” filed on Feb. 22, 2017. International Patent Application Serial No. PCT/CN2017/074386 claims priority to Chinese Patent Application No. 201610037849.5, filed on Jan. 20, 2016. The entire contents of each of the above-cited ...

Synthesis of Carbamate or Urea Compounds

The invention pertains to the synthesis of carbamate and urea compounds. In particular the invention is directed to the synthesis of carbamate and urea compounds which may be used in the production of compounds that are used to stabilize nitrocellulose. The method of the invention comprises preparing a carbamate or urea derivative comprising reacting an amine and a carbonate or carbamate in the presence of an ionic liquid. 2. Method according to claim 1 , wherein the catalyst comprises an ionic liquid.3. Method according to claim 2 , wherein the ionic liquid comprises a cation and an anion and wherein the cation is a N claim 2 ,N-dialkyl imidazolium claim 2 , preferably a 1-alkyl-3-methylimidazolium claim 2 , preferably 1-ethyl-3-methylimidazolium or 1-butyl-3-methylimidazolium (BMIm) and/or the anion is selected from the group consisting of hydroxide claim 2 , chloride claim 2 , bromide claim 2 , iodate claim 2 , acetate claim 2 , hexafluorophosphate claim 2 , tetrafluoroborate and combinations thereof claim 2 , preferably the anion is a hydroxide or a chloride.4. Method according to claim 1 , wherein the catalyst comprises a non-nucleophilic base claim 1 , preferably a superbase claim 1 , more preferably a superbase selected from the group consisting of amidines claim 1 , phosphazenes and guanidines claim 1 , even more preferably amidines claim 1 , most preferably 1 claim 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU).5. Method according to claim 1 , wherein Aris a phenyl claim 1 , optionally substituted with one or more halide claim 1 , alkoxy claim 1 , nitro claim 1 , sulfonate claim 1 , ester claim 1 , amide claim 1 , carboxylate and Aris Aror a phenyl and is optionally substituted with one or more halide claim 1 , alkoxy claim 1 , nitro claim 1 , sulfonate claim 1 , ester claim 1 , amide claim 1 , carboxylate claim 1 , preferably both Arand Arare phenyl such that the amine according to formula II is diphenylamine.6. Method according to claim 1 , wherein X is a C- ...

Augmenting Moieties for Anti-Inflammatory Compounds

Augmented or synergized anti-inflammatory constructs are disclosed including terpenes covalently conjugated with other anti-inflammatory molecules such as nonsteroidal anti-inflammatory drugs, vanilloids, amino acids and polyamines; and anti-inflammatory molecules covalently conjugated with specific amino acids. For the latter, further conjugation with a choline bioisostere further augments the anti-inflammatory activity. 2. (canceled)31. The conjugate of (d) or (f) claim 1 , wherein said terpenes are the same terpene.41. The conjugate of (d) or (f) claim 1 , wherein said terpenes are different terpenes.51. The conjugate of (b) or (e) claim 1 , wherein said vanilloids are the same vanilloid.61. The conjugate of (b) or (e) claim 1 , wherein said vanilloids are different vanilloids.7. (canceled)8. A method of increasing the potency of an anti-inflammatory compound claim 1 , comprising conjugating said anti-inflammatory compound with another anti-inflammatory compound via a carbamate linkage claim 1 , wherein said anti-inflammatory compounds are independently selected from the group consisting of anti-inflammatory terpenes claim 1 , anti-inflammatory vanilloids claim 1 , anti-inflammatory polyamines and anti-inflammatory amino acids.9. (canceled)10. The method of claim 8 , wherein said terpenes are independently selected from the group consisting of thymol claim 8 , carvacrol claim 8 , menthol claim 8 , geraniol claim 8 , nerol claim 8 , farnesol and perillyl alcohol.11. The method of claim 10 , comprising two terpenes which are the same.12. The method of claim 10 , comprising two terpenes which are different.13. The method of claim 8 , comprising two vanilloids which are the same.14. The method of claim 8 , comprising two vanilloids which are different.15. The method of claim 8 , wherein the structure of the conjugate is selected from the group consisting of Formulae 1 A claim 8 , 2A claim 8 , 3A claim 8 , 4A claim 8 , 5A claim 8 , 6A claim 8 , and 7A:(a) Formula 1A, ...

Ketamine derivatives and compositions thereof

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain.

NITRIFICATION INHIBITORS

The present invention relates to novel nitrification inhibitors of formula I. Moreover, the invention relates to the use of these novel nitrification inhibitors for reducing nitrification, as well as agrochemical mixtures and compositions comprising the nitrification inhibitors. Further encompassed by the present invention are methods for reducing nitrification comprising the treatment of plants, soil and/or loci with said nitrification inhibitors, and methods for treating a fertilizer or a composition by applying said nitrification inhibitor. 116-. (canceled)18: The compound of claim 17 , wherein in said compound of formula I claim 17 , A is phenyl or a 6-membered hetaryl claim 17 , preferably phenyl claim 17 , wherein the aromatic ring may in each case be unsubstituted or may be partially or fully substituted by substituents claim 17 , which are independently of each other selected from R.19: The compound of claim 17 , wherein in said compound of formula I claim 17 , Rand Rboth represent hydrogen.20: The compound of claim 17 , wherein in said compound of formula I claim 17 , Ris hydrogen claim 17 , C-C-haloalkyl or ethinylhydroxymethyl claim 17 , and preferably Ris hydrogen.21: The compound of claim 17 , wherein in said compound of formula I claim 17 , R claim 17 , if present claim 17 , is{'sup': a', 'b', 'c', '1', 'c', '1', 'c', '1', 'c', '1', 'a', 'b', '2', '1', '2', '1', 'a', 'b', 'g', 'd', 'e', 'f, 'sub': 2', '2', '1', '6', '2', '6', '1', '4', '1', '4', '2', '4', '1', '2', '2', '4, '(i) halogen, CN, NRR, OR, C(═Y)R, C(═Y)OR, C(═Y)SR, C(═Y)NRR, YC(═Y)R, YC(═Y)NRR, NRN═C(R)(R), S(═O)R, NO, C-C-alkyl, C-C- C-C-haloalkyl, C-C-alkoxy, C-C-alkynyl-C-C-hydroxyalkyl, C-C-alkynyloxy;'}{'sub': 2', '4', '2', '4', '1', '4', '2', '4, 'sup': 1', 'c', '2', '1', 'c, '(ii) C-C-alkenylene-C(═Y)R, C-C-alkenylene-Y—C(═Y)R, wherein the C-C-alkylene or C-C-alkenylene chain may in each case be unsubstituted or may be partially or fully substituted by CN or halogen;'}{'sup': 'h', '( ...

PRODRUGS OF PHENOLIC TRPV1 AGONISTS

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity. 4. The compound of or , wherein m is 1.5. The compound of any one of - , wherein X is —O—.6. The compound of any one of - , wherein X is —N(R)—.7. The compound of any one of - , wherein X is NH.8. The compound of or , wherein m is 0.9. The compound of any one of - , wherein Rand Rare independently selected from hydrogen and unsubstituted Calkyl.10. The compound of any one of - , wherein Rand Rare hydrogen.13. The compound of claim 12 , wherein A is O.14. The compound of any one of - claim 12 , wherein Ris independently selected from unsubstituted Calkyl claim 12 , —Calkyl-OH claim 12 , —Calkyl-C(═O)OH claim 12 , —Calkyl-C(═O)NH claim 12 , —Calkyl-N(H)C(═NH)NH claim 12 , —Calkyl-(phenyl) claim 12 , —Calkyl-(4-hydroxyphenyl) claim 12 , and —Calkyl-(heteroaryl).15. The compound of any one of - claim 12 , wherein Rand Rare independently selected from hydrogen and unsubstituted Calkyl.16. The compound of any one of - claim 12 , wherein Rand Rare hydrogen.17. The compound of any one of - claim 12 , wherein n is 1.18. The compound of any one of - claim 12 , wherein n is 2.21. The compound of claim 20 , wherein each A is O.22. The compound of or claim 20 , wherein each Z is —O—.23. The compound of or claim 20 , wherein each Z is —N(R)—.24. The compound of claim 23 , wherein each Ris independently hydrogen or unsubstituted Calkyl.25. The compound of any one of - claim 23 , wherein each Rand Rare independently selected from hydrogen claim 23 , and unsubstituted or substituted Calkyl.26. The compound of any one of - claim 23 , wherein each n is 1.27. The compound of any one of - claim 23 , wherein each n is 2.30. The compound of or claim 23 , wherein Rand Rare hydrogen.31. The compound of any one of - claim 23 , wherein n is 1.32. The compound of any one of - ...

TREATING AND PREVENTING DISEASES BY MODULATING CELL MECHANICS

Described are methods of treating or preventing a disease in a subject treatable by modulating cell mechanics. The method includes administering to a subject having or at risk for such a disease a pharmaceutical composition. comprising an agent selected from the group comprising a salt, solvate, or stereoisomer of compound (VIII) or its derivatives or a mixture of their constituents, where the compound has the formula: 2. The method of wherein myosin II is activated in the subject compared to a reference subject that has not been administered the effective amount of compound (V).3. The method of claim 1 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 1 , parenteral claim 1 , intranasal claim 1 , sublingual claim 1 , rectal claim 1 , and transdermal administration.4. The method of claim 1 , further comprising the step of administering a bioactive agent.6. The method of claim 4 , wherein the bioactive agent is a chemotherapy agent.7. The method of wherein the subject has a disease that is treated or prevented by modulating the cell mechanics of the subject.8. The method of wherein the disease is cancer.9. The method of wherein the cancer is pancreas or kidney cancer.12. The method of wherein myosin II is activated in the subject compared to a reference subject that has not been administered the effective amount of compound (VIII).13. The method of claim 11 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 11 , parenteral claim 11 , intranasal claim 11 , sublingual claim 11 , rectal claim 11 , and transdermal administration.14. The method of claim 11 , further comprising the step of administering a bioactive agent.16. The method of claim 14 , wherein the bioactive agent is a chemotherapy agent.17. The method of wherein the subject has a disease that is treated or prevented by modulating the cell mechanics of the subject.18. The method of wherein the ...

POLYMER PHOTOPOLYMERIZATION SENSITIZER

To provide a photopolymerization sensitizer which will not cause problems of dusting or coloring of a cured product by bleeding of additives such as the photopolymerization sensitizer on the surface e.g. by blooming at the time of photo-curing or during storage of the cured product, and which imparts a practically sufficient photo-curing rate. 110-. (canceled)1314-. (canceled)15. A photopolymerization initiator composition claim 11 , comprising the photopolymerization sensitizer of claim 11 , and a photopolymerization initiator.16. A photopolymerizable composition claim 15 , comprising the photopolymerization initiator composition of claim 15 , and a photocationic polymerizable compound.17. A photopolymerizable composition claim 15 , comprising the photopolymerization initiator composition of claim 15 , and a photoradical polymerizable compound. The present invention relates to an oligomer of a 9,10-bis(substituted oxy)anthracene compound, its production method, and a photopolymerization sensitizer containing an oligomer of a 9,10-bis(substituted oxy)anthracene compound.A photo-curing resin polymerizable by active energy rays such as ultraviolet rays or visible rays, which is quickly cured and can thereby remarkably reduce the amount of an organic solvent used as compared with a thermosetting resin, is superior in that the working environment can be improved and the environmental burden can be reduced. A conventional photo-curing resin by itself lacks polymerization initiation function and usually requires a photopolymerization initiator so as to be cured. The photopolymerization initiator may, for example, be an alkylphenone polymerization initiator such as hydroxyacetophenone or benzophenone, an acylphosphine oxide photopolymerization initiator or an onium salt (Patent Documents 1, 2 and 3). If an onium salt initiator is used among such photopolymerization initiators, an onium salt has light absorption in the vicinity of from 225 nm to 350 nm and has no absorption ...

Compounds which have a protective activity with respect to the action of toxins and of viruses with an intracellular mode of action

The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells.

INHIBITORS OF FATTY ACID AMIDE HYDROLASE (FAAH) ENZYME WITH IMPROVED ORAL BIOAVAILABILITY AND THEIR USE AS MEDICAMENTS

Described herein, inter alia, are compositions and methods useful for inhibiting fatty acid amide hydrolase. 4. (canceled)6. The compound of claim 1 , wherein Ris unsubstituted C-Ccycloalkyl or unsubstituted 3 to 8 membered heterocycloalkyl.7. (canceled)8. (canceled)9. The compound of claim 1 , wherein Ris independently halogen or —OCHX.10. The compound of claim 1 , wherein Ris —C(O)NRR.11. The compound of claim 1 , wherein Ris —SONRR.12. (canceled)13. The compound of claim 1 , wherein Ris hydrogen or unsubstituted C-Calkyl.14. (canceled)15. The compound of claim 1 , wherein Ris hydrogen or unsubstituted C-Calkyl.16. The compound of claim 1 , wherein Ris —SOR.17. (canceled)18. The compound of claim 16 , wherein Ris unsubstituted methyl.19. (canceled)20. (canceled)21. The compound of claim 1 , wherein Ris cyclobutyl claim 1 , cyclopentyl claim 1 , or cyclohexyl;{'sup': '2', 'sub': '2', 'Ris —F or —OCHF;'}{'sup': '3', 'sub': 2', '2', '2', '2', '2', '2', '2', '2, 'Ris —SONH, —SONHMe, —SONMe, —CONH, —CONHMe, —CONMe, or —SOMe; and'}z is 1.22. (canceled)25. The compound of claim 1 , wherein the compound has an oral bioavailability of greater than 35% in a subject.26. (canceled)27. (canceled)28. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , of .3040.-. (canceled)42. (canceled)43. (canceled)44. (canceled)4672.-. (canceled) This application claims the benefit of U.S. Provisional Patent Application No. 61/976,439 filed on Apr. 7, 2014, which is incorporated herein by reference in its entirety and for all purposes.This invention was made with government support under grant no. DA031387, awarded by the National Institutes of Health. The Government has certain rights in the invention.Described herein are certain O-arylcarbamate inhibitors of the fatty acid amide hydrolase (FAAH) enzyme that showed, unexpectedly, an improved oral bioavailability, their methods of ...

DNP and DNP Prodrug Treatment of Neuromuscular, Neurodegenerative, Autoimmune, Developmental, Traumatic Brain Injury, Concussion, Dry Eye Disease, Hearing Loss and/or Metabolic Diseases

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment. 146-. (canceled)48. The composition of claim 47 , wherein the prodrug is stable at a pH of 1-2.49. The composition of claim 47 , wherein the prodrug is stable at a pH of 4.5.50. The composition of claim 47 , wherein the prodrug is stable at a pH of 5-9.51. A depot nanoparticle formulation comprising the composition of .52. A method of treatment of neuromuscular diseases claim 47 , neuromuscular degenerative diseases claim 47 , muscle wasting diseases claim 47 , neurodegenerative diseases claim 47 , autoimmune diseases claim 47 , developmental diseases claim 47 , traumatic diseases of CNS claim 47 , hearing loss ...

N-Substituted Carbamic Acid Ester Production Method, Isocyanate Production Method Using Such N-Substituted Carbamic Acid Ester, and Composition for Transfer and Storage of N-Substituted Carbamic Acid Ester Comprising N-Substituted Carbamic Acid Ester and Aromatic Hydroxy Compound

The present invention is a method for producing an N-substituted carbamic acid ester derived from an organic amine from an organic amine, a carbonic acid derivative and a hydroxy composition containing one or more types of hydroxy compounds, wherein the organic amine, the carbonic acid derivative and the hydroxy composition are reacted using a urethane production reaction vessel provided with a condenser, a gas containing the hydroxy composition, the compound having the carbonyl group derived from the carbonic acid derivative, and an ammonia formed as a by-product in the reaction, is introduced into the condenser provided in the urethane production reaction vessel, and the hydroxy composition and the compound having the carbonyl group derived from the carbonic acid derivative are condensed, and wherein a stoichiometric ratio of a hydroxy compound contained in the condensed hydroxy composition to the condensed compound having the carbonyl group derived from the carbonic acid derivative is 1 or more, and a ratio of number of carbonyl groups (—C(═O)—) contained in the compound having the carbonyl group derived from the carbonic acid derivative and number of ammonia molecules contained in the ammonia recovered as a gas from the condenser is 1 or less. 126.-. (canceled)28. The composition according to claim 27 , wherein the N-substituted carbamic acid-O—Ar ester is prepared from the organic amine claim 27 , the carbonic acid derivative and the aromatic hydroxy composition claim 27 , and the composition comprises at least one type of compound that is urea and/or a carbamic acid ester and/or biuret and/or a compound that comprises a terminal biuret group claim 27 , (—NH—(C═O)—NH—(C═O)—NH) claim 27 , is derived from an organic amine and is formed in a reaction of the organic amine claim 27 , the carbonic acid derivative and the aromatic hydroxy composition.29. The composition according to claim 27 , comprising a carbonic acid ester derived from the aromatic hydroxy ...

AROMATIC SUBSTITUTED ETHANE-CORE MONOMERS AND POLYMERS THEREOF FOR VOLUME BRAGG GRATINGS

The disclosure provides recording materials including aromatic substituted ethane-core derivatized monomers and polymers for use in volume Bragg gratings, including, but not limited to, volume Bragg gratings for holography applications. Several structures are disclosed for monomers and polymers for use in Bragg gratings applications, leading to materials with higher refractive index, low birefringence, and high transparency. The disclosed derivatized monomers and polymers thereof can be used in any volume Bragg gratings materials, including two-stage polymer materials where a matrix is cured in a first step, and then the volume Bragg grating is written by way of a second curing step of a monomer. 2. The compound of claim 1 , wherein the substituent comprises one or more linking groups selected from —Calkyl- claim 1 , —O—Calkyl- claim 1 , —Calkenyl- claim 1 , —O—Calkenyl- claim 1 , —Ccycloalkenyl- claim 1 , —O—Ccycloalkenyl- claim 1 , —Calkynyl- claim 1 , —O—Calkynyl- claim 1 , —Caryl- claim 1 , —O—C— claim 1 , -aryl- claim 1 , —O— claim 1 , —S— claim 1 , —S(O)— claim 1 , —C(O)— claim 1 , —C(O)O— claim 1 , —OC(O)— claim 1 , —C(O)S— claim 1 , —SC(O)— claim 1 , —OC(O)O— claim 1 , —N(R)— claim 1 , —C(O)N(R)— claim 1 , —N(R)C(O)— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —SC(O)N(R)— claim 1 , —N(R)C(O)S— claim 1 , —N(R)C(O)N(R)— claim 1 , —N(R)C(NR)N(R)— claim 1 , —N(R)S(O)— claim 1 , —S(O)N(R)— claim 1 , —S(O)O— claim 1 , —OS(O)— claim 1 , —OS(O)O— claim 1 , —O(O)P(OR)O— claim 1 , (O)P(O—) claim 1 , —O(S)P(OR)O— claim 1 , and (S)P(O—) claim 1 ,wherein w is 1 or 2, and R is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl.3. The compound of claim 1 , wherein the substituent comprises one or more linking groups selected from —(CH)— claim 1 , 1 claim 1 ,2 disubstituted phenyl claim 1 , 1 claim 1 ,3 disubstituted phenyl claim 1 , 1 claim 1 ,4 disubstituted phenyl claim 1 , disubstituted glycidyl claim 1 , trisubstituted ...

AROMATIC SUBSTITUTED METHANE-CORE MONOMERS AND POLYMERS THEREOF FOR VOLUME BRAGG GRATINGS

The disclosure provides recording materials including aromatic substituted methane-core derivatized monomers and polymers for use in volume Bragg gratings, including, but not limited to, volume Bragg gratings for holography applications. Several structures are disclosed for monomers and polymers for use in Bragg gratings applications leading to materials with higher refractive index, low birefringence, and high transparency. The disclosed derivatized monomers and polymers thereof can be used in any volume Bragg gratings materials, including two-stage polymer materials where a matrix is cured in a first step, and then the volume Bragg grating is written by way of a second curing step of a monomer. 2. The compound of claim 1 , wherein any one of R claim 1 , R claim 1 , R claim 1 , and Rindependently comprises one or more linking groups selected from —Calkyl- claim 1 , —O—Calkyl- claim 1 , —Calkenyl- claim 1 , —O—Calkenyl- claim 1 , —Ccycloalkenyl- claim 1 , —O—Ccycloalkenyl- claim 1 , —Calkynyl- claim 1 , —O—Calkynyl- claim 1 , —Caryl- claim 1 , —O—C— claim 1 , -aryl- claim 1 , —O— claim 1 , —S— claim 1 , —S(O)— claim 1 , —C(O)— claim 1 , —C(O)O— claim 1 , —OC(O)— claim 1 , —C(O)S— claim 1 , —SC(O)— claim 1 , —OC(O)O— claim 1 , —N(R)— claim 1 , —C(O)N(R)— claim 1 , —N(R)C(O)— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —SC(O)N(R)— claim 1 , —N(R)C(O)S— claim 1 , —N(R)C(O)N(R)— claim 1 , —N(R)C(NR)N(R)— claim 1 , —N(R)S(O)— claim 1 , —S(O)N(R)— claim 1 , —S(O)O— claim 1 , —OS(O)— claim 1 , —OS(O)O— claim 1 , —O(O)P(OR)O— claim 1 , (O)P(O—) claim 1 , —O(S)P(OR)O— claim 1 , and (S)P(O—) claim 1 ,{'sup': 'b', 'wherein w is 1 or 2, and Ris independently hydrogen, optionally substituted alkyl, or optionally substituted aryl.'}3. The compound of claim 1 , wherein any one of R claim 1 , R claim 1 , R claim 1 , and Rindependently comprises one or more terminal groups selected from hydrogen claim 1 , optionally substituted alkyl claim 1 , optionally substituted ...

ANTHRAQUINONE DERIVATIZED MONOMERS AND POLYMERS FOR VOLUME BRAGG GRATINGS

The disclosure provides recording materials including anthraquinone derivatized monomers and polymers for use in volume Bragg gratings, including, but not limited to, volume Bragg gratings for holography applications. Several structures are disclosed for anthraquinone derivatized monomers and polymers for use in Bragg gratings applications, leading to materials with higher refractive index, low birefringence, and high transparency. The disclosed anthraquinone derivatized monomers and polymers thereof can be used in any volume Bragg gratings materials, including two-stage polymer materials where a matrix is cured in a first step, and then the volume Bragg grating is written by way of a second curing step of a monomer. 2. The compound of claim 1 , wherein the substituent comprises one or more linking groups selected from —Calkyl- claim 1 , —O—Calkyl- claim 1 , —Calkenyl- claim 1 , —O—Calkenyl- claim 1 , —Ccycloalkenyl- claim 1 , —O—Ccycloalkenyl- claim 1 , —Calkynyl- claim 1 , —O—Calkynyl- claim 1 , —Caryl- claim 1 , —O—C— claim 1 , -aryl- claim 1 , —O— claim 1 , —S— claim 1 , —S(O)— claim 1 , —C(O)— claim 1 , —C(O)O— claim 1 , —OC(O)— claim 1 , —C(O)S— claim 1 , —SC(O)— claim 1 , —OC(O)O— claim 1 , —N(R)— claim 1 , —C(O)N(R)— claim 1 , —N(R)C(O)— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —SC(O)N(R)— claim 1 , —N(R)C(O)S— claim 1 , —N(R)C(O)N(R)— claim 1 , —N(R)C(NR)N(R)— claim 1 , —N(R)S(O)— claim 1 , —S(O)N(R)— claim 1 , —S(O)O— claim 1 , —OS(O)— claim 1 , —OS(O)O— claim 1 , —O(O)P(OR)O— claim 1 , (O)P(O—) claim 1 , —O(S)P(OR)O— claim 1 , and (S)P(O—) claim 1 ,{'sup': 'b', 'wherein w is 1 or 2, and Ris independently hydrogen, optionally substituted alkyl, or optionally substituted aryl.'}3. The compound of claim 1 , wherein the substituent comprises one or more terminal groups selected from hydrogen claim 1 , optionally substituted alkyl claim 1 , optionally substituted heteroalkyl claim 1 , optionally substituted alkenyl claim 1 , optionally substituted ...

AROMATIC SUBSTITUTED ALKANE-CORE MONOMERS AND POLYMERS THEREOF FOR VOLUME BRAGG GRATINGS

The disclosure provides recording materials including aromatic substituted alkane-core derivatized monomers and polymers for use in volume Bragg gratings, including, but not limited to, volume Bragg gratings for holography applications. Several structures are disclosed, including Formula I. When used in Bragg gratings applications, the monomers and polymers disclosed lead to materials with higher refractive index, low birefringence, and high transparency. The disclosed derivatized monomers and polymers can be used in any volume Bragg gratings materials, including two-stage polymer materials where a matrix is cured in a first step, and then the volume Bragg grating is written by way of a second curing step of a monomer. 2. The compound of claim 1 , wherein the substituent comprises one or more linking groups selected from —Calkyl- claim 1 , —O—Calkyl- claim 1 , —Calkenyl- claim 1 , —O—Calkenyl- claim 1 , —Ccycloalkenyl- claim 1 , —O—Ccycloalkenyl- claim 1 , —Calkynyl- claim 1 , —O—Calkynyl- claim 1 , —Caryl- claim 1 , —O—C— claim 1 , -aryl- claim 1 , —O— claim 1 , —S— claim 1 , —S(O)— claim 1 , —C(O)— claim 1 , —C(O)O— claim 1 , —OC(O)— claim 1 , —C(O)S— claim 1 , —SC(O)— claim 1 , —OC(O)O— claim 1 , —N(R)— claim 1 , —C(O)N(R)— claim 1 , —N(R)C(O)— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —SC(O)N(R)— claim 1 , —N(R)C(O)S— claim 1 , —N(R)C(O)N(R)— claim 1 , —N(R)C(NR)N(R)— claim 1 , —N(R)S(O)— claim 1 , —S(O)N(R) claim 1 , —S(O)O— claim 1 , —OS(O)— claim 1 , —OS(O)O— claim 1 , —O(O)P(OR)O— claim 1 , (O)P(O—) claim 1 , —O(S)P(OR)O— claim 1 , and (S)P(O—) claim 1 ,{'sup': 'b', 'wherein w is 1 or 2, and Ris independently hydrogen, optionally substituted alkyl, or optionally substituted aryl.'}3. The compound of claim 1 , wherein the substituent comprises one or more linking groups selected from —(CH)— claim 1 , 1 claim 1 ,2 disubstituted phenyl claim 1 , 1 claim 1 ,3 disubstituted phenyl claim 1 , 1 claim 1 ,4 disubstituted phenyl claim 1 , disubstituted ...

Tetra-substituted ndga derivatives via ether bonds and carbamate bonds and their synthesis and pharmaceutical use

Disclosed are nordihydroguaiaretic acid derivative compounds including various end groups bonded by a carbon atom or heteroatom though a side chain bonded to the respective hydroxy residue O groups by an ether bond or a carbamate bond, pharmaceutical compositions, methods of making them, and methods of using them and kits including them for the treatment of diseases and disorders, in particular, diseases resulting from or associated with a virus infection, such as HIV infection, HPV infection, or HSV infection, an inflammatory disease, such as various types of arthritis and inflammatory bowel diseases, a metabolic disease, such as diabetes, a vascular disease, such as hypertension and macular degeneration, or a proliferative disease, such as diverse types of cancers.

PRODRUGS OF PHENOLIC TRPV1 AGONISTS

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity. 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein Ris hydrogen and Ris H or substituted or unsubstituted alkyl.5. The compound of claim 4 , wherein X is —N(R)—.6. The compound of claim 5 , wherein Rand Rgroups on adjacent atoms claim 5 , together with the atoms to which they are attached claim 5 , form a substituted or unsubstituted heterocycloalkyl group.7. The compound of claim 6 , wherein the heterocycloalkyl group is a substituted or unsubstituted pyrrolidine ring claim 6 , substituted or unsubstituted piperidine ring claim 6 , or substituted or unsubstituted piperazine ring.1018.-. (canceled)20. (canceled) This application claims benefit of U.S. Provisional Application No. 62/084,515, filed on Nov. 25, 2014, which is herein incorporated by reference in its entirety.Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate the transient receptor potential vanilloid 1 receptor (TRPV1) activity.In one aspect, described herein is a compound having the structure of Formula (I):wherein:Y is a phenolic TRPV1 agonist, wherein the hydrogen atom of the phenolic hydroxyl group is replaced by a covalent bond to —C(O)—X—(C(R)(R))—Z;X is —C(R)(R)—, —O—, —N(R)— or —S—;n is an integer from 1 to 10;Z is —NRRor —COH;Ris hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, and each Rand Ris each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted acyl, or Rand Rtogether with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl group, or two Ror Rgroups on adjacent carbon atoms, together with the carbon atoms to which ...

BENZODICYCLOALKANE DERIVATIVE, PREPARATION METHOD AND USE THEREOF

It is provided herein a benzobicycloalkane derivative, and a preparation method and use thereof. In particular, it is provided herein a compound of Formula (I), or a pharmaceutically acceptable salt, stereoisomer or solvate thereof, a preparation method, and a use thereof in preparation of drugs for treating pain. 2. The compound or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or stereoisomer thereof of claim 1 , wherein Rand Rare hydrogen.3. The compound or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or stereoisomer thereof of claim 1 , wherein Ris hydrogen claim 1 , Calkyl claim 1 , Ccycloalkyl or —((CH)—O)—CH;{'sub': 2', '1-10', '3-8', '6-10', '2', 'n2', 'm2', '3, 'b': '13', 'Ris Calkyl, Ccycloalkyl, Caryl, 5 to 6 membered single heteroaryl ring, 4 to 6 membered saturated single heterocycle, spiro, spiroheterocycle, bridged ring, bridged heterocycle or —((CH) O)—CH; wherein n1 and n2 are each independently 2, 3 or 4; and, m1 and m2 are each independently 1, 2, 3, 4, 5, 6, 7, 8 or 9;'}{'sub': 1', '2, 'or Rand R, together with the nitrogen atom to which they are attached, form a 4 to 6 membered saturated single heterocycle; and'}{'sub': a0', 'b0', '1-8', '1-8', '1-8', '3-8', '3-8', '2-10', '2-10', '1-8', '6-10', '1-10', '1-10', '1-10', 'a0', 'b0', 'a0', 'b0', '1-8', '1-8', '1-8, 'the alkyl, cycloalkyl, aryl, 4 to 6 membered saturated single heterocycle, 5 to 6 membered single heteroaryl ring, spiro, spiroheterocycle, bridged ring, and bridged heterocycle are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of NRR, halogen, acetyl, hydroxy, hydroxymethyl, hydroxyethyl, carboxyl, Calkyl, Calkoxy, halogenated Calkyl, Ccycloalkyl, Ccycloalkoxy, Calkenyl, Calkynyl, halogenated Calkoxy, Caryl, 4 to 6 membered saturated single heterocycle, —C(O)Calkyl, —C(O)OCalkyl, —OC(O)Calkyl, and —CONRR; and, Rand Rare each independently hydrogen, Calkyl, and Calkyl substituted with Calkoxy.'}4. The ...

ENANTIOSELECTIVE SYNTHESIS OF ALPHA-QUATERNARY MANNICH ADDUCTS BY PALLADIUM-CATALYZED ALLYLIC ALKYLATION

This invention provides enantioenriched Mannich adducts with quaternary stereogenic centers and novel methods of preparing the compounds. Methods include the method for the preparation of a compound of formula (I): 163-. (canceled)65. The method of claim 64 , wherein the transition metal catalyst comprises a transition metal selected from palladium claim 64 , nickel claim 64 , and platinum.66. The method of claim 64 , wherein the transition metal catalyst further comprises a chiral ligand.67. The method of claim 64 , wherein the compound represented by formula (Ia) has about 80% ee or greater.68. The method of claim 64 , wherein the compound represented by formula (Ia) has about 85% ee or greater.69. The method of claim 64 , wherein the compound represented by formula (Ia) has about 90% ee or greater. This Application is a Continuation of U.S. patent application Ser. No. 14/972,475, filed Dec. 17, 2015, which claims the benefit of U.S. Provisional Application 62/093,982, filed Dec. 18, 2014, the contents of both of which are incorporated herein by reference.This invention was made with Government support under Grant Number R01GM080269, awarded by the National Institutes of Health. The Government has certain rights in the invention.The Mannich reaction, first discovered in the early 20th century, is among the most robust reactions known to produce nitrogen-containing compounds. In a classic intermolecular Mannich reaction, an aldehyde, an amine and an α-acidic carbonyl compound react to form a β-amino carbonyl compound. Recent progress in this area, including modified imine donors and well-explored catalyst systems, has made available a wide variety of asymmetric α-functionalizations of carbonyl compounds. However, to date, asymmetric Mannich-type reactions to establish α-quaternary carbonyl compounds have been limited to specialized substrate classes.There exists a need for methods that enable access to α-quaternary Mannich Adducts, particularly enantioselective ...

Use of cannabidiol prodrugs in topical and transdermal administration with microneedles

Described herein are microneedle drug delivery systems comprising a pharmaceutical compositions comprising pharmaceutically active agents (e.g., cannabidiol and prodrugs of cannabidiol) and microneedle arrays suitable for local and systemic delivery of the active agent to a mammal. Also described herein are methods of using a microneedle transdermal or topical drug delivery systems comprising pharmaceutical compositions, comprising cannabidiol and prodrugs of cannabidiol, and microneedle arrays in the treatment disease, including pancreatitis and pancreatic cancer.

Processes For Preparing A Polymeric Compound

The present invention provides methods for preparing a polymeric compound of Formula I: The present invention was supported, in part, by funds from the U.S. Government (SBIR Phase 1 grant No. 1R43HL090113-01) and the U.S. Government may therefore have certain rights in the invention.The present invention is directed, in part, to methods for preparing a polymeric salicylamide compound and/or pharmaceutically acceptable salts thereof, as well as to useful intermediates for the preparation of the polymeric salicylamide compound and/or pharmaceutically acceptable salts thereof.The polymeric salicylamide compound of Formula I:and/or pharmaceutically acceptable salts thereof are useful, for example, as pharmaceutical agents for inhibiting angiogenesis (see, WO 2005/123660). Given the importance of the compound of Formula I and/or pharmaceutically acceptable salts thereof as pharmaceutical agents, effective synthetic methods for preparing the compound and its pharmaceutically acceptable salts is of great import. This invention is directed to this, as well as other, important ends.The present invention provides, in part, methods for preparing a compound of Formula I:or pharmaceutically acceptable salt thereof, comprising:a) removing the Cbz groups from a compound of Formula II:or pharmaceutically acceptable salt thereof, under a hydrogenation/hydrogenolysis condition to form the compound of Formula I, or pharmaceutically acceptable salt thereof; andb) optionally isolating the compound of Formula I, or pharmaceutically acceptable salt thereof.In some embodiments, the hydrogenation/hydrogenolysis condition comprises using a metal catalyst. In some embodiments, the metal catalyst is Pd/C. In some embodiments, the reaction yield in step a) is greater than about 85%.In some embodiments, the methods further comprise:c) removing the Boc group from a compound of Formula III:or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula II, ...

MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF

Multitarget inhibitors of the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having a specific carbamate moiety on the meta or ortho position of the A ring of a substituted biphenyl core and having an halogen in the ortho position of the B ring of the biphenyl core. Also concerns the therapeutical application of the multitarget inhibitors, in particular, in the prevention and treatment of cancer. 2. A compound according to wherein Ris F claim 1 ,{'sub': 2', '1', '6', '5', '6', '5', '1', '6', '6', '7', '8', '7', '8', '1', '10', '1', '10', '3', '9', '3', '9', '7', '8, 'Ris a (C-C)alkyl substituted with OH, COOH or is a group —CHR—(C═O)—R, wherein Ris H, or an optionally substituted (C-C)alkyl, and Ris —OH or NRR, where Rand Rare independently H, an optionally substituted group selected from (C-C)alkyl, hetero(C-C)alkyl, (C-C)cycloalkyl, hetero(C-C)cycloalkyl, aryl, and heteroaryl, or if taken together with the N atom to which they are attached, Rand Rform an optionally substituted N-heterocycle or an optionally substituted heteroaryl with the N atom to which they are each attached.'}3. A compound according to wherein Ris a group —CHR—(C═O)—R claim 1 , wherein{'sub': 5', '1', '6, 'Ris H, or (C-C)alkyl, and'}{'sub': 6', '7', '8', '7', '8', '1', '10', '1', '10', '3', '9', '3', '9', '7', '8, 'Ris —OH or NRR, where Rand Rare independently H, an optionally substituted group selected from (C-C)alkyl, hetero(C-C)alkyl, (C-C)cycloalkyl, hetero(C-C)cycloalkyl, aryl, and heteroaryl, or if taken together with the N atom to which they are attached, Rand Rform an optionally substituted N-heterocycle or an optionally substituted heteroaryl with the N atom to which they are each attached.'}4. A compound according to wherein Rand Rare independently an optionally substituted group selected from C-Calkyl claim 1 , hetero(C-C)alkyl claim 1 , (C-C)cycloalkyl(C-C)alkyl claim 1 , aryl(C-C)alkyl claim 1 , heteroaryl(C-C)alkyl and hetero(C- ...

INHIBITORS OF FATTY ACID AMIDE HYDROLASE (FAAH) ENZYME WITH IMPROVED ORAL BIOAVAILABILITY AND THEIR USE AS MEDICAMENTS

Described herein, inter alia, are compositions and methods useful for inhibiting fatty acid amide hydrolase. 6. The method of claim 1 , wherein Ris unsubstituted C-Ccycloalkyl or unsubstituted 3 to 8 membered heterocycloalkyl.7. (canceled)8. (canceled)9. The method of claim 1 , wherein Ris independently halogen or —OCHX.10. The method of claim 1 , wherein Ris —C(O)NRR.11. The method of claim 1 , wherein Ris —SONRR.12. (canceled)13. The method of claim 1 , wherein Ris hydrogen or unsubstituted C-Calkyl.14. (canceled)15. The method of claim 1 , wherein Ris hydrogen or unsubstituted C-Calkyl.16. The method of claim 1 , wherein Ris —SOR.17. The method of claim 16 , wherein Ris unsubstituted C-Calkyl or unsubstituted 2 to 4 membered heteroalkyl.18. (canceled)19. (canceled)20. (canceled)21. The method of claim 1 , wherein Ris cyclobutyl claim 1 , cyclopentyl claim 1 , or cyclohexyl;{'sup': '2', 'sub': '2', 'Ris —F or —OCHF;'}{'sup': '3', 'sub': 2', '2', '2', '2', '2', '2', '2', '2, 'Ris —SONH, —SONHMe, —SONMe, —CONH, —CONHMe, —CONMe, or —SOMe; and'}z is 1.22. (canceled)23. (canceled)2572.-. (canceled)74. The method of claim 1 , wherein the disease is a wound.75. The method of claim 1 , wherein the disease is overactive bladder. This application claims the benefit of U.S. Provisional Patent Application No. 61/976,439 filed on Apr. 7, 2014, which is incorporated herein by reference in its entirety and for all purposes.This invention was made with government support under grant no. DA031387, awarded by the National Institutes of Health. The Government has certain rights in the invention.Described herein are certain O-arylcarbamate inhibitors of the fatty acid amide hydrolase (FAAH) enzyme that showed, unexpectedly, an improved oral bioavailability, their methods of preparation, their formulations as medicaments, and their therapeutic application for the treatment of pathologies, conditions and disorders which would clinically benefit from inhibition of the activity of the ...

META-SUBSTITUTED BIPHENYL PERIPHERALLY RESTRICTED FAAH INHIBITORS

The present invention provides methods of making and using peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH). The present invention provides compounds and compositions that suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). The present invention also sets forth methods for inhibiting FAAH as well as methods for treating conditions such as, but not limited to, pain, inflammation, immune disorders, dermatitis, mucositis, the over reactivity of peripheral sensory neurons, neurodermatitis, and an overactive bladder. Accordingly, the invention also provides compounds, methods, and pharmaceutical compositions for treating conditions in which the selective inhibition of peripheral FAAH (as opposed to CNS FAAH) would be of benefit. 2. The compound of claim 1 , wherein Rand Rare each H.3. The compound of claim 1 , wherein m and n are each 0.4. The compound of claim 1 , wherein Ris hydroxy claim 1 , carboxy claim 1 , or hydroxymethyl.5. The compound of claim 1 , wherein claim 1 , Ris unsubstituted.6. The compound of claim 1 , wherein Ris cyclohexyl.7. The compound of claim 1 , wherein claim 1 , Rand Rare each H or Ris methyl claim 1 , ethyl claim 1 , trifluoromethyl or trifluoroethyl.8. The compound of claim 1 , wherein m is 0 and n is 0 or 1.9. The compound of claim 1 , wherein m is 1 and n is 0 or 1.10. The compound of claim 1 , wherein each member of the R claim 1 , R claim 1 , R claim 1 , and RMarkush groups is unsubstituted.11. The compound of claim 1 , wherein Ris hydroxy or an alcohol group or a physiologically hydrolyzable ester of the hydroxyl or alcohol group.12. The compound of claim 11 , wherein the physiologically hydrolysable ester is of the formula —OC(O)R claim 11 , —CHOC(O)Ror —CHCHOC(O)R. and Ris substituted or unsubstituted hydrocarbyl.13. The compound of claim 1 , wherein Ris or —C(O)OR claim 1 , and Ris hydrogen or substituted or unsubstituted hydrocarbyl.14. The compound of claim 1 , ...

COMPOUNDS AND METHODS FOR TREATING MAMMALIAN GASTROINTESTINAL MICROBIAL INFECTIONS

Disclosed are compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound selectively inhibits a parasitic IMPDH versus a host IMPDH. Also disclosed are pharmaceutical compositions comprising one or more compounds of the invention. Related methods of treating various parasitic and bacterial infections in mammals are disclosed. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants. 2423. A method of killing or inhibiting the growth of a microbe claims 1 , comprising the step of contacting said microbe with an effective amount of a compound of any one of -.25. The method of claim 24 , wherein said microbe is a protozoan or a bacterium.26Toxoplasma, Eimeria, Cryptosporidium, Plasmodium, Babesia, Theileria, Neospora, Sarcocystis, Giardia, Entamoeba, Tritrichomonas, Leishmania, Trypanosoma, Helicobacter, Borrelia, Salmonella, Shigella, Yersinia, Streptococcus, Campylobacter, Arcobacter, Bacteroides, Fusobacterium, Burkholderia, Clostridia, Neisseria, MycobacteriumAcinetobacter.. The method of claim 24 , wherein said microbe is a protozoan or a bacterium selected from the group consisting of the genera claim 24 , and27Cryptosporidium, Entamoeba, LeishmaniaTrypanosoma.. The method of claim 25 , wherein said microbe is a protozoan; and said protozoan is selected from the group consisting of the genera and28Cryptosporidium.. The method of claim 27 , wherein said protozoan is selected from the genus29Cryptosporidium parvum, Cryptosporidium hominis. The method of claim 27 , wherein said protozoan is claim 27 , or both.30Acinetobacter, Arcobacter, Bacillus, Bacteroides, Borrelia, Brachyspira, Brucella, Burkholderia, Campylobacter, Clostridia, Coxiella, Enterococcus, Erysipelothrix, Francisella, Fusobacterium, Helicobacter, Lactobacillus, Listeria, Mycobacterium, ...

CARBAMATE COMPOUNDS AND METHODS OF USE IN DISEASES OF THE NERVOUS SYSTEM

In general, among other things, compounds of Formula I are provided: 1. (canceled)34-. (canceled)5. The compound of in which Ris I or F.68-. (canceled)9. A method of treatment of an amyloid disease in a subject comprising administering a therapeutically effective amount of a compound of to the subject.10. A method of diagnosis of Alzheimer's disease in a subject comprising administering a diagnostically effective amount of a compound of to the subject.11. The method of in which the amyloid disease is Alzheimer's disease.12. The method of in which the amyloid disease is Parkinson's disease.13. A method of diagnosis of multiple sclerosis in a subject comprising administering a diagnostically effective amount of a compound of to the subject.148. A method of diagnosis of brain tumour in a subject comprising administering a diagnostically effective amount of a compound of any of - to the subject.15. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.17. The method according to claim 16 , wherein said condition is associated with Alzheimer's disease.18. The method according to claim 16 , wherein said compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier.19. The method according to claim 18 , wherein a total daily dose of from about 0.0003 to about 30 mg/kg of body weight is administered.20. A method of inhibiting butyrylcholinesterase activity in a patient which comprises administering a therapeutically effective amount of a compound of to the patient. A method of treatment of an amyloid disease in a subject comprising administering a therapeutically effective amount of a compound of to the subject.21. (canceled)23. The method according to claim 22 , wherein said amyloid disease is Alzheimer's disease.24. The method according to claim 22 , wherein said amyloid disease is Parkinson's disease.25. The method according to claim 22 , wherein said amyloid disease is Huntington's ...

PRO-DRUGS AND RELATED METHODS

The invention relates to Pro-drugs, comprising red-ox-sensitive cleavage sites. The compounds may be utilized in medical practice for targeting of si RNA, antisense oligonucleotides or protein-based therapeutics to the cytoplasmatic compartment of cells both in vitro or in vivo, in a subject in need. 10. A Pro-drug according to claim 1 , wherein either Y or Z claim 1 , or both Y and Z comprise a drug claim 1 , selected from a small-molecule drug claim 1 , a peptide claim 1 , a therapeutic protein and an oligonucleotide claim 1 , selected from single-stranded or double-stranded RNA claim 1 , DNA claim 1 , siRNA or ASO.11. A pharmaceutical composition claim 1 , comprising a pro-drug according to claim 1 , and pharmaceutically-acceptable carrier(s) or salt(s).12. A method for treatment of a medical disorder claim 11 , said method comprising administration to a patient in need claim 11 , therapeutically effective amounts of a pharmaceutical composition according to .13. A method for redox-dependent cleavage of a Pro-drug claim 11 , said method comprising (A). Incorporation of a ROSS in the structure of the Pro-drug claim 11 , wherein said ROSS has the following structural motifs: (i). a cyclic hydrocarbon disulfide moiety; (ii). A carbonyl group claim 11 , positioned at 5-7 atoms from at least one of the sulfur atoms; and (iii). A leaving group claim 11 , attached to the carbonyl group through carbamate claim 11 , ester or amide bonds; (B). Maintaining the Pro-drug initially in an oxidative environment; and (C). Transferring the Pro-drug into an ambient reductive environment claim 11 , thereby providing the required conditions for ring opening claim 11 , cleavage of the pro-drug claim 11 , and release of the active drug.14. A method for redox-dependent cleavage of a Pro-drug claim 11 , said method comprising (A). Incorporation in the structure of the Pro-drug a ROSS according to any of Formulae I claim 11 , II claim 11 , III claim 11 , IIIa claim 11 , IIIb claim 11 , IV ...

METHOD FOR ANALYZING ENANTIOMER

Enantiomers may be analyzed by: 1. A method for analyzing an enantiomer , comprising (1) to (3) below:(1) reacting a mixture of a first compound and a second compound that are a pair of enantiomers with an axially chiral compound that is one of a pair of axially chiral isomers, to generate a derivative mixture containing a first derivative obtained by a reaction of the first compound with the axially chiral compound and a second derivative obtained by a reaction of the second compound with the axially chiral compound;(2) separating said first derivative and said second derivative in the derivative mixture; and(3) detecting the separated first derivative and second derivative by mass spectrometry.4. The method according to claim 2 , wherein the reactive group is a nucleophilic group claim 2 , an electrophilic group claim 2 , or a group containing at least one of a nucleophilic group and an electrophilic group.5. The method according to claim 4 , wherein the reactive group is:{'sub': 1', '6', '1', '6, '(1) a carbonyl group having a leaving group (wherein the leaving group is selected from the group consisting of Cto Calkyloxy, Cto Calkylcarbonyloxy, a halogen atom, succinimidooxy, phenyloxy having an electron-withdrawing group, imidazolyl, and triazolyl);'}(2) a nucleophilic group selected from the group consisting of an amino group, a hydrazino group, a hydroxy group, and a sulfanyl group;(3) an electrophilic group selected from the group consisting of a maleimide group, an acryloylamino group, a methacryloylamino group, and a formyl group; or(4) a group containing any of the groups (1) to (3).7. The method according to claim 3 , wherein the group having a charged atom or a chargeable atom is:(1) an optionally substituted amino group;(2) an optionally substituted ammonio group;(3) an optionally substituted guanidino group;(4) an optionally substituted guanidinium group;(5) an optionally substituted imino group;(6) an optionally substituted iminium group;(7) an ...

PROCESS FOR PREPARING SUBSTITUTED ISATOIC ACID ANHYDRIDE COMPOUNDS AND DERIVATIVES THEREOF

The present invention relates to a process for preparing substituted isatoic acid anhydride compounds of the formula (I) 115.-. (canceled)20. The process according to claim 16 , in which{'sup': '1', 'Ris Cl; and'}{'sup': '2', 'sub': '3', 'Ris CH.'}21. The process according to claim 16 , in which the solvent is selected from aromatic hydrocarbon solvents or polar aprotic solvents.22. The process according to claim 16 , in which the solvent is selected from toluene claim 16 , ethylbenzene claim 16 , o-xylene claim 16 , m-xylene claim 16 , p-xylene claim 16 , chlorbenzene claim 16 , or a mixture thereof claim 16 , preferably toluene.23. The process according to claim 16 , in which the solvent is selected from acetonitrile claim 16 , n-butyl acetate and tetrahydrofurane.24. The process according to claim 16 , in which the reaction of step (b) is carried out at a temperature between 60 and 120° C.26. The compound of formula (II) according to claim 25 , in which{'sup': '1', 'Ris Cl, Br, I, or CN; and'}{'sup': '2', 'sub': '3', 'Ris CH, and'}{'sup': 'Ar', 'sub': 3', '2, 'Ris CH, Cl, NOand n is 0, 1, 2, 3, 4 or 5.'} The present invention relates to a process for preparing substituted isatoic acid anhydride compounds and derivatives thereof, in particular anthranilamides. It also relates to the use of these preparing substituted isatoic acid anhydride compounds for preparing anthranilamide derivatives that are useful pesticides. Therefore, substituted isatoic acid anhydride compounds are important precursors for anthranilamide derivatives. Such compounds find use as pesticides, especially as insecticides, which are disclosed, for example, in WO 01/70671, WO 03/015518, WO 03/015519, WO 03/016284, WO 03/016300, WO 03/024222, WO2003/062221, WO2003/027099, WO2004/067528, WO2003/106427, WO 06/000336; WO 06/068669, WO 07/043677, WO2008/126933, WO2008/126858, and WO2008/130021, and in WO2007/006670, WO2013/024009, WO2013/024010, WO2013/024003, WO2013/024004, WO2013/024005, WO2013/ ...

Compounds Which Have a Protective Activity with Respect to the Action of Toxins and of Viruses with an Intracellular Mode of Action

The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells. 2. The method as claimed in claim 1 , characterized in that said compound of and/or Ris a hydrogen atom.4. (canceled)5. The method as claimed in claim 1 , characterized in that said compound of general formula (I) is selected from the group consisting ofCompound 1: N-benzyladamantylamine;Compound 2: N-(2-bromobenzyl)adamantylamine;Compound 3: N-(3-bromobenzyl)adamantylamine;Compound 4: N-(4-bromobenzyl)adamantylamine;Compound 5: N-(3-fluorobenzyl)adamantylamine;Compound 6: N-(3-hydroxybenzyl)adamantylamine;Compound 7: N-(2-methoxybenzyl)adamantylamine;Compound 8: N-(3-methoxybenzyl)adamantylamine;Compound 9: N-(4-methoxybenzyl)adamantylamine;Compound 10: N-(2-nitrobenzyl)adamantylamine;Compound 11: N-(4-nitrobenzyl)adamantylamine;Compound 12: N-(4-carbethoxybenzyl)adamantylamine;Compound 13: 4-bromo-2-((1-adamantylino)methyl)phenol;Compound 14: N-(2-bromo-5-nitrobenzyl)adamantylamine;Compound 15: N-[(2-methoxy-5-bromo)benzyl]adamantylamine;Compound 16: N-((pyridin-2-yl)methyl)adamantylamine;Compound 17: N-((pyridin-3-yl)methyl)adamantylamine;Compound 18: N-((pyridin-4-yl)methyl)adamantylamine;Compound 19: N-((5-methylfuran-2-yl)methy)adamantylamine;Compound 20: N-((5-methylthiophen-2-yl)methyl)cyclohexanamine;Compound 21: N-[(3-furyl)methyl]adamantylamine;Compound 22: N-((1-methyl-1H-imidazol-5-yl)methy)adamantylamine;Compound 23: N-[(5-N-methylimidazolyl)methyl]adamantylamine;Compound 24: Benzo[d][1,3]dioxol-4-yl)methyl)adamantylamine;Compound 25: N-((5-nitrobenzo[d][1,3]dioxol-6-yl)methyl)adamantylamine;Compound 26: N-((quinolin-3-yl)methyl)adamantylamine;Compound 27: N-((quinolin-4-yl) ...

POLYCYCLIC COMPOUNDS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS

The present invention relates to soluble epoxide hydrolase (sEH) inhibitors of formula (I) to processes for their obtention and to their therapeutic indications. 2. A compound according to wherein Grepresents a methylene group.3. A compound according to wherein Grepresents an oxygen atom.4. A compound according to wherein Grepresents a radical selected from the group consisting of —NH—(CH)— and —(CH)— claim 1 , m is an integer from 0 to 6 and n is an integer from 1 to 7.5. A compound according to wherein Grepresents a radical-NH—(CH)— and m is an integer from 0 to 6.6. A compound according to wherein claim 1 , when Gis selected from the group consisting of —NH—(CH)— and —O—(CH)— claim 1 , m has a value of 0 and wherein Gis —(CH)— n has a value of 1.7. A compound according to wherein Ris selected from the group consisting of substituted or unsubstituted phenyl claim 1 , substituted or unsubstituted cyclohexyl and substituted or unsubstituted piperidinyl.8. A compound according to wherein Ris selected from the group consisting of hydrogen atoms claim 1 , fluorine atoms claim 1 , chlorine atoms claim 1 , methyl claim 1 , hydroxyl and C-Calkoxy.9. A compound according to wherein Rand Rare radicals which may be identical or different and which are independently selected from the group consisting of hydrogen atoms claim 1 , halogen atoms claim 1 , C-Cacyl claim 1 , trifluoromethyl (CF) claim 1 , trifluoromethoxy (OCF) claim 1 , nitro (NO) claim 1 , amino (NH) and C-Calkoxy.10. A compound according to wherein Ris hydrogen and Ris a radical selected from the group consisting of hydrogen atoms claim 1 , halogen atoms claim 1 , C-Cacyl claim 1 , trifluoromethyl (CF) claim 1 , trifluoromethoxy (OCF) claim 1 , nitro (NO) claim 1 , amino (NH) and C-Calkoxy.11. The compound according to claim 1 , which is selected from the group consisting of:i. p-tolyl (9-methyl-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-yl)carbamateii. 1-(9-methyl-5,6,8,9,10,11-hexahydro-7H- ...

KETAMINE DERIVATIVES AND COMPOSITIONS THEREOF

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain. 2. The method of claim 1 , wherein administering comprises orally administering.3. The method of claim 1 , wherein the pain is selected from back pain claim 1 , cancer pain claim 1 , carpal tunnel syndrome pain claim 1 , chronic pain claim 1 , diabetic peripheral neuropathy claim 1 , fibromyalgia claim 1 , migraine claim 1 , myofascial pain claim 1 , neuropathic pain claim 1 , neuralgia claim 1 , osteoarthritis claim 1 , peripheral neuropathy claim 1 , postoperative pain claim 1 , regional pain syndrome claim 1 , rheumatoid arthritis pain claim 1 , sciatica claim 1 , scoliosis pain claim 1 , spinal cord injury pain claim 1 , spinal stenosis claim 1 , trigeminal neuralgia claim 1 , and traumatic pain.7. The method of claim 1 , wherein the compound is selected from:1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetylglycinate (3);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl (tert-butoxycarbonyl)glycinate (4);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl (tert-butoxycarbonyl)-L-valinate (5);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl 2-(3-methyloxetan-3-yl)acetate (6);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetyl-L-alaninate (7);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl acetyl-L-valinate (8);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl 1-methylpiperidine-4-carboxylate (17);1-((((S)-1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)ethyl isobutyrylglycinate (19);(S)-(((1-(2-chlorophenyl)-2-oxocyclohexyl)(methyl)carbamoyl)oxy)methyl 2-(3-methyloxetan-3-yl)acetate (22);1 ...

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1 comprising administering to a subject in need thereof a compound described here. 2. The compound of claim 1 , wherein Ris 3-fluorophenyl.3. The compound of claim 1 , wherein:{'sup': '1', 'Ris selected from cyclohexyl, cyclopentyl, cycloheptyl, 3,3-difluorocyclobutyl, 4,4,-difluorocyclohexyl, and bicyclo[2.2.1]heptanyl; and'}{'sup': '4', 'Ris selected from 1-(methylmethoxycarbonylamino)ethyl, 1,2,3,4-tetrahydroquinolin-1-yl, 1-ethoxycarbonylpiperidin-2-yl, 1-ethoxycarbonylpyrrolidin-2-yl, 1H-benzimidazol-1-ylmethyl, 1H-indazol-3-ylmethyl, indolin-1-ylmethyl, 1H-indol-3-ylmethyl, 1H-indol-5-ylmethyl, 1H-pyrrolo[2,3-b]pyridine-3-ylmethyl, 1H-pyrrolo[3,2-b]pyridin-3-ylmethyl, 1-methoxycarbonylpiperidin-2-yl, 1-methoxycarbonylpyrrolidin-2-yl, 2-fluoropyridin-3-ylaminomethyl, 2-imino-4-fluoropyridin-1-ylmethyl, 2-methoxyphenylaminomethyl, 2-methyl-1H-benzimidazol-1-ylmethyl, 2-methylimidazol-1-ylmethyl, 2-trifluoromethyl-1H-imidazol-1-yl, 3-cyanophenylaminomethyl, 3-fluoropyridin-2-ylaminomethyl, 3-methoxyphenylaminomethyl, 4-(1,3,4-oxadiazole-2-yl)phenylaminomethyl, 4-(dimethylaminocarbonyloxy)phenylmethyl, 4,5-dichloroimidazol-1-ylmethyl, 4-cyanophenylaminomethyl, 4-fluorophenylaminomethyl, 4-fluoropyridin-2-ylaminomethyl, 4-hydroxyphenylmethyl, 4-methoxycarbonylmorpholin-3-yl, 4-methoxycarbonylpiperazin-1-ylmethyl, 4-methoxyphenylaminomethyl, 4-methylcarbonyloxyphenylmethyl, 5-fluoropyridin-2-aminomethyl, 5-fluoropyridin-2-oxymethyl, 6-fluoropyridin-3-ylaminomethyl, benzomorpholin-4-ylmethyl, methoxycarbonylaminomethyl, methylmethoxycarbonylaminomethyl, methylphenylaminomethyl, phenylaminomethyl, pyridin-2-oxymethyl, pyridin-2-ylaminomethyl, pyridin-2-yloxymethyl, pyridin-3-oxymethyl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, thiazol-4-ylmethyl, and thien-2-ylmethyl.'}4. The compound of claim 1 , wherein the compound is selected from any one of Compound numbers 104 claim 1 ...

INHIBITION OF RESPIRATORY COMPLEX III BY LIGANDS THAT INTERACT WITH A REGULATORY SWITCH

The present invention provides methods for inhibiting respiratory complex III in a cell. The present invention also provides methods for treating cancer in a subject. 14. The method of claim 1 , wherein the cell is a cancer cell.15. The method of claim 14 , wherein the cancer cell is in a subject.16. The method of claim 15 , further comprising administering to the subject an amount of the compound effective to inhibit respiratory complex III in the cancer cell. The present application is a division of U.S. application Ser. No. 16/531,511, filed Aug. 5, 2019, which is a continuation of International Patent Application No. PCT/US2018/017638, filed Feb. 9, 2018, which claims priority to U.S. Provisional Appln. No. 62/457,684, filed Feb. 10, 2017, the disclosures of which are herein incorporated by reference in their entirety for all purposes.This invention was made with Government support under Grant No. GM054052 awarded by the National Institutes of Health (NIH). The Government has certain rights in the invention.Ideally, a smart anti-cancer drug should discriminate between cancer and normal cells. One of the recently discovered biochemical variations in cancer cells that distinguish them from normal cells is a higher basal level of reactive oxygen species (ROS), which makes the cancer cells more susceptible to ROS-induced apoptosis (Szatrowski and Nathan (1991) 51:794; Kawanishi et al. (2006) 387:365; Toyokuni et al. (1995) 358:1; and Trachootham et al. (2009) 8:579). However, since cancer cells can adapt to such oxidative stress by up-regulating antioxidant production (Tiligada (2006) 13:S115), to make use of such a mechanism, a drug should induce rapid production and accumulation of ROS and trigger apoptosis in cancer cells before anti-oxidant up-regulation takes effect.The mitochondrial electron transport chain (METC) is one of the major sources of ROS in the cell (Adam-Vizi and Chinopoulos (2006) 27:639; and Lenaz (2001) 52:159), and respiratory complex III (also ...

PRODRUGS OF PHENOLIC TRPV1 AGONISTS

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity. 3. The compound of claim 2 , wherein Ris unsubstituted alkyl or alkyl substituted with one or more groups selected from halogen claim 2 , —CN claim 2 , —NH claim 2 , —NH(CH) claim 2 , —N(CH) claim 2 , —OH claim 2 , —COH claim 2 , —COalkyl claim 2 , —C(═O)NH claim 2 , —C(═O)NH(alkyl) claim 2 , —C(═O)N(alkyl) claim 2 , —S(═O)NH claim 2 , —S(═O)NH(alkyl) claim 2 , —S(═O)N(alkyl) claim 2 , alkyl claim 2 , cycloalkyl claim 2 , fluoroalkyl claim 2 , heteroalkyl claim 2 , alkoxy claim 2 , fluoroalkoxy claim 2 , heterocycloalkyl claim 2 , aryl claim 2 , heteroaryl claim 2 , aryloxy claim 2 , alkylthio claim 2 , arylthio claim 2 , alkylsulfoxide claim 2 , arylsulfoxide claim 2 , alkylsulfone claim 2 , and arylsulfone.4. The compound of any one of - claim 2 , wherein Ris alkoxy.5. The compound of any one of - claim 2 , wherein Ris unsubstituted alkyl.8. The compound of any one of - claim 2 , wherein Z is —NRR.9. The compound of any one of - claim 2 , wherein Ris hydrogen and Ris H or substituted or unsubstituted alkyl.10. The compound of any one of - claim 2 , wherein X is —N(R)—.11. The compound of claim 10 , wherein Rand Rgroups on adjacent atoms claim 10 , together with the atoms to which they are attached claim 10 , form a substituted or unsubstituted heterocycloalkyl group.12. The compound of claim 11 , wherein the heterocycloalkyl group is a substituted or unsubstituted pyrrolidine ring claim 11 , substituted or unsubstituted piperidine ring claim 11 , or substituted or unsubstituted piperazine ring.13. The compound of claim 11 , wherein the heterocycloalkyl group is an unsubstituted pyrrolidine ring claim 11 , unsubstituted piperidine ring claim 11 , or unsubstituted piperazine ring.15. The compound of claim 10 , wherein Ris hydrogen.16. The compound ...

PRODRUGS OF PHENOLIC TRPV1 AGONISTS

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity. 2. The compound of any one of claim 1 , wherein Z is —NRR.3. The compound of claim 2 , wherein Ris hydrogen and Ris hydrogen or substituted or unsubstituted alkyl.4. The compound of claim 3 , wherein Rand Rgroups on adjacent atoms claim 3 , together with the atoms to which they are attached claim 3 , form a substituted or unsubstituted heterocycloalkyl group.5. The compound of claim 4 , wherein the heterocycloalkyl group is a substituted or unsubstituted pyrrolidine ring claim 4 , substituted or unsubstituted piperidine ring claim 4 , or substituted or unsubstituted piperazine ring.6. The compound of claim 4 , wherein the heterocycloalkyl group is an unsubstituted pyrrolidine ring claim 4 , unsubstituted piperidine ring claim 4 , or unsubstituted piperazine ring.8. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , pharmaceutically acceptable solvate claim 1 , or hydrate thereof claim 1 , and a pharmaceutically acceptable diluent claim 1 , excipient or binder.9. A method of treating pain in a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , pharmaceutically acceptable solvate claim 1 , or hydrate thereof. This application is a continuation of U.S. application Ser. No. 15/529,076, filed on May 23, 2017, which was National Phase of PCT/US2015/062531, filed on Nov. 24, 2015, which was a continuation inpart of U.S. patent application Ser. No. 14/743,375, filed on Jun. 18, 2015, which claims benefit of U.S. Provisional Application No. 62/084,515, filed on Nov. 25, 2014, all of which are herein incorporated by reference in their entirety.Described herein are compounds, pharmaceutical ...

Polyisocyanate Composition and Isocyanate Polymer Composition

The present invention relates to a polyisocyanate composition comprising, on the basis of the total mass of the polyisocyanate composition, 97 weight % or more of a polyisocyanate, and 2.0 mass ppm or more and 1.0×10mass ppm or less of a compound having at least one unsaturated bond in which the compound is a different compound from the polyisocyanate, or 5.0 mass ppm or more and 2.0×10mass ppm or less of at least one inactive compound selected from the group consisting of a hydrocarbon compound, an ether compound, a sulfide compound, a halogenated hydrocarbon compound, a Si-containing hydrocarbon compound, a Si-containing ether compound, and a Si-containing sulfide compound. 120-. (canceled)22. The composition according to claim 21 , further comprising a compound having at least one unsaturated bond claim 21 ,wherein the unsaturated bond is a carbon-carbon double bond or a carbon-oxygen double bond,the carbon-carbon double bond is not a carbon-carbon double bond that constitutes an aromatic ring, andsaid compound having at least one unsaturated bond and said compound represented by formula (1) are different.23. The composition according to claim 22 , wherein the compound having at least one unsaturated bond comprises a carbonic acid derivative.24. The composition according to claim 23 , wherein the carbonic acid derivative is at least one carbonic acid ester selected from the group consisting of dimethyl carbonate claim 23 , diethyl carbonate claim 23 , dibutyl carbonate claim 23 , dipentyl carbonate claim 23 , and dihexyl carbonate; or an N-unsubstituted carbamic acid ester.25. The composition according to claim 21 , further comprising at least one compound selected from the group consisting of a hydrocarbon compound claim 21 , an ether compound claim 21 , a sulfide compound claim 21 , a halogenated hydrocarbon compound claim 21 , a Si-containing hydrocarbon compound claim 21 , a Si-containing ether compound claim 21 , and a Si-containing sulfide compound.27. The ...

ACTIVATORS OF MYOSIN II FOR MODULATING CELL MECHANICS

The present invention discloses small molecule compounds as activators of myosin II by promoting its assembly and recruitment to contractile structures in the cell and methods of using such compounds. These compounds are useful to modulate cell and tissue mechanics. This class of molecules, which affect cell mechanics either by activating the contractile system of the cell or modulating cytokinesis, will be used for therapeutic and tissue engineering applications. 2. The method of claim 1 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 1 , parenteral claim 1 , intranasal claim 1 , sublingual claim 1 , rectal claim 1 , and transdermal administration.4. The method of claim 3 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 3 , parenteral claim 3 , intranasal claim 3 , sublingual claim 3 , rectal claim 3 , and transdermal administration.6. The method of claim 5 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 5 , parenteral claim 5 , intranasal claim 5 , sublingual claim 5 , rectal claim 5 , and transdermal administration.8. The method of claim 7 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 7 , parenteral claim 7 , intranasal claim 7 , sublingual claim 7 , rectal claim 7 , and transdermal administration.10. The compound of claim 9 , wherein the compound is administered by systemic delivery selected from the group consisting of oral claim 9 , parenteral claim 9 , intranasal claim 9 , sublingual claim 9 , rectal claim 9 , and transdermal administration.12. The compound of claim 11 , wherein the compound is administered by systemic delivery selected from the group consisting of oral claim 11 , parenteral claim 11 , intranasal claim 11 , sublingual claim 11 , rectal claim 11 , and transdermal administration.14. The compound of claim 13 ...

SUBSTITUTED TETRACYCLINE COMPOUNDS

The present invention pertains, at least in part, to novel substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for tetracycline compounds such as blocking tetracycline efflux and modulation of gene expression. 149-. (canceled)51. The method of claim 50 , wherein said tetracycline responsive state is an inflammatory disorder.52. The method of claim 51 , wherein said tetracycline responsive state is an inflammatory condition of the skin.53. The method of claim 51 , wherein said tetracycline responsive state is an inflammatory disorder caused by trauma.54. The method of claim 51 , wherein said tetracycline responsive state is an inflammatory disorder caused by radiation.55. The method of claim 50 , wherein said subject is a human.57. The method of claim 56 , wherein said tetracycline responsive state is an inflammatory disorder.58. The method of claim 57 , wherein said tetracycline responsive state is an inflammatory condition of the skin.59. The method of claim 57 , wherein said tetracycline responsive state is an inflammatory disorder caused by trauma.60. The method of claim 57 , wherein said tetracycline responsive state is an inflammatory disorder caused by radiation.61. The method of claim 56 , wherein said subject is a human. This patent application claims priority to U.S. Provisional Patent Application Ser. No. 60/530,123, filed Dec. 16, 2003; U.S. Provisional Patent Application Ser. No. 60/525,287, filed Nov. 25, 2003; and U.S. Provisional Patent Application Ser. No. 60/486,017, filed Jul. 9, 2003, all of which are entitled “Substituted Tetracycline Compounds.” The entire contents of each of the aforementioned applications are hereby incorporated herein by reference.The development of the tetracycline antibiotics was the direct result of a systematic screening of soil specimens collected from many ...

MODULATORS OF THE EIF2ALPHA PATHWAY

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2α phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory. 29.-. (canceled)10. The method of claim 1 , wherein said inflammatory disease is associated with neurological inflammation claim 1 , postoperative cognitive dysfunction claim 1 , or traumatic brain injury.11. (canceled)12. (canceled)14. (canceled)1621.-. (canceled)24. (canceled)25. (canceled)2734.-. (canceled)36. (canceled)4247.-. (canceled)50. (canceled)51. (canceled)5360.-. (canceled)62. (canceled)64. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound claim 40 , or pharmaceutically acceptable salt thereof claim 40 , of . This application is a continuation of U.S. patent application Ser. No. 14/849,428, filed Sep. 9, 2015, which is a continuation of International Patent Application No. PCT/US2014/029568, filed Mar. 14, 2014, which claims the benefit of U.S. Provisional Patent Application No. 61/787,633, filed Mar. 15, 2013, all of which are incorporated herein by reference in their entirety and for all purposes.The Sequence Listing written in file 84850-903323_ST25.TXT, created Mar. 14, 2014, 3,576 bytes, machine format IBM-PC, MS-Windows operating system, is hereby incorporated by reference.In metazoa, diverse stress signals converge at a single phosphorylation event at serine 51 of a common effector, the translation initiation factor eIF2α. This step is carried out by four eIF2α kinases in mammalian cells: PERK, which responds to an accumulation of unfolded proteins in the endoplasmic reticulum (ER), GCN2 to amino acid starvation and UV light, PKR to viral infection, and HRI to heme deficiency. This collection of signaling pathways has been termed the “integrated stress response” (ISR), as they converge on the same ...

TREATING AND PREVENTING DISEASES BY MODULATING CELL MECHANICS

Described are methods of treating or preventing a disease in a subject treatable by modulating cell mechanics. The method includes administering to a subject having or at risk for such a disease a pharmaceutical composition. comprising an agent selected from the group comprising a salt, solvate, or stereoisomer of compound (VIII) or its derivatives or a mixture of their constituents, where the compound has the formula: 110.-. (canceled)12. The method of wherein myosin II is activated in the subject compared to a reference subject that has not been administered the effective amount of compound (VIII).13. The method of claim 11 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 11 , parenteral claim 11 , intranasal claim 11 , sublingual claim 11 , rectal claim 11 , and transdermal administration.14. The method of claim 11 , further comprising the step of administering a bioactive agent.16. The method of claim 14 , wherein the bioactive agent is a chemotherapy agent.17. The method of wherein the subject has a disease that is treated or prevented by modulating the cell mechanics of the subject.18. The method of wherein the disease is cancer.19. The method of wherein the cancer is pancreas or kidney cancer.2031.-. (canceled)33. An in vivo claim 18 , large-scale and high-throughput screening method for identifying cell mechanical modulator claim 18 , the screening method comprising the steps of: (a) obtaining cells and placing the cells on multiple-well substrate plates for cytokinesis; (b) contacting the cells on multiple-well substrate plates with compound candidates; and (c) monitoring and analyzing the cytokinesis and the growth of the cells.34Dictyostelium discoideum. The screening method of claim 33 , wherein the cells are from strains.35Dictyostelium discoideum. The screening method of claim 34 , wherein strains comprise wild type and mutants.36. (canceled)37. The method of claim 32 , further comprising the ...

MODULATORS OF THE EIF2ALPHA PATHWAY

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2α phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory. 212.-.14. (canceled)1621.-. (canceled)2425.-. (canceled)2734.-. (canceled)3637.-. (canceled)4247.-. (canceled)5051.-. (canceled)5360.-. (canceled)6263.-. (canceled)64. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound claim 40 , or pharmaceutically acceptable salt thereof claim 40 , of .65. The method of claim 13 , wherein the plasmacytoma is a subcutaneous plasmacytoma. This application is a continuation of U.S. patent application Ser. No. 15/614,278, filed on Jun. 5, 2017, now allowed, which is a continuation of U.S. patent application Ser. No. 14/849,428, filed Sep. 9, 2015, now U.S. Pat. No. 9,708,247, issued on Jul. 18, 2017, which is a continuation of International Patent Application No. PCT/US2014/029568, filed Mar. 14, 2014, which claims the benefit of U.S. Provisional Patent Application No. 61/787,633, filed Mar. 15, 2013, all of which are incorporated herein by reference in their entirety and for all purposes.The Sequence Listing written in file 048536-539C02US_SL_ST25.TXT, created May 21, 2019, 3,608 bytes, machine format IBM-PC, MS-Windows operating system, is hereby incorporated by reference.In metazoa, diverse stress signals converge at a single phosphorylation event at serine 51 of a common effector, the translation initiation factor eIF2α. This step is carried out by four eIF2α kinases in mammalian cells: PERK, which responds to an accumulation of unfolded proteins in the endoplasmic reticulum (ER), GCN2 to amino acid starvation and UV light, PKR to viral infection, and HRI to heme deficiency. This collection of signaling pathways has been termed the “integrated stress response” (ISR), as they converge on the ...

PRODRUGS OF FENCAMFAMINE

Disclosed herein are pharmaceutical compositions comprising fencamfamine or fencamfamine related prodrug derivatives for targeted therapeutic applications and methods of synthesizing the compositions. 2. The prodrug composition of claim 1 , wherein R1 is selected from the group consisting of Me claim 1 , Et claim 1 , tBu claim 1 , 5-isopropyl-2-methylphenyl claim 1 , and 2-isopropyl-5-methylphenyl.3. The prodrug composition of claim 1 , wherein R2 and R6 are independently selected from the group consisting of H and Me.4. The compound of claim 3 , wherein R3 is independently selected from optionally substituted C1-26 alkanoyl.5. The compound of claim 4 , wherein R3 is from C12 to C18 in chain length.6. The prodrug composition of claim 1 , wherein R3 is selected from the group consisting of acetyl claim 1 , pivaloyl claim 1 , butyryl claim 1 , capryloyl claim 1 , decanoyl claim 1 , lauroyl claim 1 , and stearoyl.7. The compound of claim 1 , wherein X is —O(CHR2)OR3.8. The compound of claim 7 , wherein R2 is independently selected from hydrogen claim 7 , optionally substituted C1-6 alkyl.12. The prodrug composition of claim 1 , wherein R4 is —CH2CH2COOH.13. The prodrug composition of claim 1 , wherein (A)n is selected from the group consisting of Val claim 1 , Lys claim 1 , Gly claim 1 , Gly-Gly claim 1 , Val-Val claim 1 , Gly-Ala claim 1 , Phe claim 1 , Phe-Phe claim 1 , Ala-Gly claim 1 , and Lys-Lys.15. (canceled)16. The prodrug composition comprising the compound of wherein the prodrug has an increased plasma or blood concentration of the released N-ethyl-3-phenylbicyclo[2.2.1]heptan-2-amine when administered orally as compared to when it is administered intravenously and when the unconjugated drug is administered in equimolar amounts.17. The prodrug composition comprising the compound of wherein the prodrug composition is in the form comprising a tablet claim 1 , a capsule claim 1 , elixir claim 1 , emulsion solution claim 1 , suspension solution claim 1 , or syrup ...

Substituted benzyloxy-phenylmethylcarbamate derivatives

The present invention relates to novel substituted benzyloxy-phenylmethylcarbamate derivatives, processes for their preparation, and their use in medicaments, especially for the prophylaxis and treatment of diseases associated with Cold Menthol Receptor 1 (CMR-1) activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

6-Dimethylaminomethyl-1-phenyl-cyclo-hexane compounds as pharmaceutical agents

6-Dimethylaminomethyl-1-phenyl cyclohexane derivs. of formula (I) are new: R<1> = H, OH, Cl or F; R<2>, R<3> = H, 1-4C alkyl, benzyl, CF3, OH, OCH2Ph, 1-4C alkoxy, Cl or F; R<4> = H, Me, PO(1-4C alkoxy)2, CO(1-5C alkoxy), CO-NH-C6H4-(1-3C alkyl), CO-C6H4-R<5>, CO-(1-5C alkyl), CO-CHR<6>-NHR<7> or opt. substd. pyridyl, thienyl, thiazolyl or phenyl; R<5> = OC(O)-(1-3C alkyl) in ortho position, or CH2-N(R<8>)2 in meta- or para-position; R<8> = 1-4C alkyl; or NR<8>R<8> = 4-morpholino; R<6>, R<7> = H or 1-6C alkyl; provided that: (i) one of R<2>, R<3> = H; (ii) when R<2> and R<3> = H, then R<4> is not Me if R<1> = H, OH or Cl; and (iii) R<4> is not H when R<1> = OH.

1-phenyl-3-dimethylamino-propane compounds with pharmacological activity

6-Dimethylaminomethyl-1-phenyl-cyclohexane compounds as active pharmaceutical ingredients

Process for antibody directed enzyme prodrug therapy

Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs are substrates for carboxypeptidase G2 (CPG2) and yield more active cytotoxic drugs than known products of CPG2 catalysed reactions.

LXR modulators

The invention provides compounds, compositions and methods for modulating the effects of LXR in a cell. The compounds and compositions are useful both as diagnostic indicators of LXR function and as pharmacologically active agents. The compounds and compositions find particular use in the treatment of disease states associated with cholesterol metabolism, particularly atherosclerosis and hypercholesterolemia.

Chemical compounds

Prodrugs for antibody directed enzyme prodrug therapy

Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs substrates for carboxypeptidase G2 (CPG2) and yield more cytotoxic drugs than known products of CPG2 catalysed

Lxr modulators

The invention provides compounds, compositions and methods for modulating the effects of LXR in a cell. The compounds and compositions are useful both as diagnostic indicators of LXR function and as pharmacologically active agents. The compounds and compositions find particular use in the treatment of disease states associated with cholesterol metabolism, particularly atherosclerosis and hypercholesterolemia.

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6-диметиламинометил-1-фенилциклогексановые соединения в качестве фармацевтически действующих веществ и способы их получения (варианты)

Изобретение относится к новым 6-диметиламинометил-1-фенилциклогексановым соединениям общей формулы 1 в виде оснований или их физиологически приемлемых солей, проявляющим анальгетическую активность и предназначенным для получения фармацевтической композиции, а также к способам их получения. В общей формуле I радикалы имеют следующие значения: R 1 представляет собой Н, ОН, Сl или F; R 2 и R 3 являются идентичными или разными и означают Н, С 1 -С 4 алкил, CF 3 , ОН, ОСН 2 -С 6 Н 5 , O-С 1 -С 4 алкил, при условии, что по крайней мере один из радикалов R 2 или R 3 означает Н; R 4 означает Н, СН 3 , СО(ОС 1 -С 5 алкил), СО-NН-С 6 H 4 -С 1 -С 3 алкил, CO-C 6 H 4 -R 5 , СО-С 1 -С 5 алкил, CO-CHR 6 -NHR 7 или незамещенную, либо замещенную С 1 -С 4 алкилом пиридиловую или фенильную группу; R 5 означает ОС(O)С 1 -С 3 алкил в орто-положении или CH 2 -N(R 8 ) 2 в мета- либо пара-положении, причем оба радикала R 8 вместе с N представляют собой 4-морфолиновый радикал; и R 6 , R 7 являются идентичными или разными и означают Н или С 1 -С 6 алкил при условии, что если оба радикала R 2 и R 3 означают Н, то R 4 не является CH 3 , если R 1 означает Н, ОН или Сl, либо R 4 не является Н, если R 1 означает ОН. Описываются также различные способы получения соединений формулы I. Например, для получения соединений, где R 1 означает ОН, диметиламинокетон формулы II подвергают взаимодействию с металлорганическим соединением формулы III, или диметиламинокетон со спироциклической ацетильной группой формулы V подвергают взаимодействию с металлорганическим соединением формулы III, с получением соединения формулы VI, которое деацетилированием переводят в соединение кетона VIII, с последующим восстановлением комплексным гидридом щелочного металла до соединения формулы I, которое после перевода в соль щелочного металла переводят в соответствующее O-алкил или O-бензилпроизводное. Описывается также способы получения соединений, где R 1 означает Н, или соединений, где R 1 означает F. 7 с. и 4 з. п. ф-лы, ...

약제학적 활성 성분으로서의 6-디메틸아미노메틸-1-페닐-사이클로헥산 화합물

Производные азотистого иприта, связанные с аминокислотами, которые являются пролекарственными субстратами для ферментов карбоксипептидазы, способ их получения, фармацевтическая композиция и двухкомпонентная система для доставки цитотоксического лекарства

Изобретение касается новых соединений формулы I, где R 1 и R 2 каждый независимо представляет хлор, бром, иод или OSO 2 Me; R 1a и R 2b - водород; R 3 и R 4 - водород; R 5a и R 5b -водород, C 1-4 -алкил, галоид; R 5a и R 5b вместе -СН= СН-СН= СН-; R 5c и R 5d - водород, циано, галоид; Х представляет O, NH, -СН 2 -; Y представляет O; Z представляет -V-W, где V представляет -СН 2 Т-, в которой Т представляет -CH 2 - или -S-; W представляет СООН, -(С=O)NR 7 R 8 , где R 7 - водород, C 1-6 -алкил и др.; R 8 - водород, и их соли. Способ получения соединений формулы I заключается в удалении защиты у соединения формулы Iа. Предложены фармацевтическая композиция, содержащая эффективное количество соединения формулы I, а также двухкомпонентная система доставки цитотоксического лекарства, содержащая антитело или его фрагмент, способные связывать определенный антиген, причем антитело или его фрагмент конъюгированы с энзимом СРG, способным превращать соединение формулы I или его соль в цитотоксическое лекарство, и содержит дополнительно соединение формулы I или его соль, превращаемые под действием энзима СРG в цитотоксическое лекарство. 4 c. и 12 з.п ф-лы, 18 табл., 1 ил. сучестьс ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ "” 2 129 542 ' (51) МПК 13) СЛ С 07С 271/54, 275/40, 237/40, 309/66, 311/51, С 070 257/04, А 61 К 31/27, 39/395, 31/17, 38/43 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 95105246/04, 23.07.1993 (30) Приоритет: 23.07.1992 СВ 9215636.3 26.05.1993 СВ 9310884.3 (46) Дата публикации: 27.04.1999 (56) Ссылки: ЦЗ 4975278 А, 1991. МО 8807378, 06.10.88. 5Ц 222373 А, 1967. 50 292965 А, 1969. КУ 94038047 АЛ, 10.06.96. (85) Дата перевода заявки РСТ на национальную фазу: 20.01.95 (86) Заявка РСТ: СВ 93101560 (23.07.93) (87) Публикация РСТ: М/О 94/02450 (03.02.94) (98) Адрес для переписки: 103735, Москва, ул.Ильинка 5/2, Союзпатент (71) Заявитель: Зенека Лимитед (СВ)}, Кэнсер Рисерч Кэмпейн Текнолоджи Лимитед (СВ) (72) ...

1-phenyl-3-dimethylamino-propane compounds having pharmacological action

COMPOSITIONS OF RESOURCES ISOCIANAT BLOCK-COPOLYMERS AND THEIR APPLICATIONS

Композиции блок-сополимеров резорцин-изоцианат получают от реакции между резорциновым соединением и по меньшей мере двумя различными изоцианатными соединениями. Композиции блок-сополимеров резорцин-изоцианат могут иметь две или более температуры деполимеризации блок-сополимера и/или характеристики плавления, которые могут обеспечить некоторые уникальные свойства, такие как улучшенная адгезия материалов для армирования каучуков, для материалов или соединений каучуков. Композиции блок-сополимеров резорцин-изоцианат могут использоваться как препараты для обработки тканей погружением и/или в каучуковых композициях с улучшенными свойствами. Resorcinol-isocyanate block copolymer compositions are prepared from the reaction between a resorcinol compound and at least two different isocyanate compounds. Resorcinol-isocyanate block copolymer compositions can have two or more block copolymer depolymerization temperatures and / or melting characteristics that can provide some unique properties such as improved adhesion of rubber reinforcement materials to rubber materials or compounds. Resorcinol-isocyanate block copolymer compositions can be used as dip formulations and / or in enhanced rubber compositions.

Method for producing isocyanate

본 발명의 목적은, 포스겐을 사용하지 않고서 이소시아네이트를 제조할 때에, 선행기술에서 보이는 여러 가지 문제점이 없고, 높은 수율로 이소시아네이트를 장기간 안정적으로 제조할 수 있는 방법을 제공하는 데에 있다. 본 발명은, 카르바민산에스테르와 방향족 히드록시 화합물을 반응시켜, 이 방향족 히드록시 화합물에서 유래하는 기를 갖는 카르바민산아릴을 얻는 공정과, 상기 카르바민산아릴을 분해 반응에 부치는 공정을 포함하는 이소시아네이트를 제조하는 방법으로서, 상기 방향족 히드록시 화합물이, 하기 식(1)으로 나타내어지는, 히드록실기의 적어도 하나의 오르토 자리에 치환기 R 1 을 갖는 방향족 히드록시 화합물인 이소시아네이트의 제조 방법을 개시한다: An object of the present invention is to provide a method capable of stably producing an isocyanate for a long time in a high yield, without various problems seen in the prior art when producing isocyanate without using phosgene. The present invention includes a step of reacting a carbamic acid ester with an aromatic hydroxy compound to obtain an aryl carbamate having a group derived from the aromatic hydroxy compound, and a step of attaching the aryl carbamate to the decomposition reaction. As a method for producing an isocyanate, a method for producing an isocyanate in which the aromatic hydroxy compound is an aromatic hydroxy compound having a substituent R 1 in at least one ortho site of the hydroxyl group represented by the following formula (1) is disclosed. : (식에서, 고리 A는 치환기를 갖더라도 좋은, 탄소수 6∼20의 단환 혹은 복수환인 방향족 탄화수소 고리를 나타내고, R 1 은 수소 원자 이외의 기로서, 탄소, 산소, 질소에서 선택되는 원자를 포함하는, 탄소수 1∼20의 지방족 알킬기, 탄소수 1∼20의 지방족 알콕시기, 탄소수 6∼20의 아릴기, 탄소수 6∼20의 아릴옥시기, 탄소수 7∼20의 아랄킬기, 또는 탄소수 7∼20의 아랄킬옥시기를 나타내며, 또한 R 1 은 A와 결합하여 고리 구조를 형성하더라도 좋음). (In Formula, Ring A represents a C6-C20 monocyclic or plural ring aromatic hydrocarbon ring which may have a substituent, R < 1> is group other than a hydrogen atom and contains the atom chosen from carbon, oxygen, and nitrogen, C1-C20 aliphatic alkyl group, C1-C20 aliphatic alkoxy group, C6-C20 aryl group, C6-C20 aryloxy group, C7-C20 aralkyl group, or C7-C20 aralkyl An oxy group, and R 1 may be bonded to A to form a ring structure).

Curcumin-Resveratrol hybrid molecule

Novel molecules based upon hybridization of curcumin and hydroxystilbenes, such as resveratrol. It is believed that these novel molecules will have special application in treating Alzheimer's Disease.

Iontophoretic delivery of curcumin and curcumin analogs for the treatment of Alzheimer's Disease

A method of delivering a curcuminoid to a patient, which includes iontophoretically delivering a charged curcuminoid across the skin of an Alzheimer's Disease patient.

Diamine Derivative, Process for Producing the Same, and Bactericide Containing the Same as Active Ingredient

본 발명에 따르면 하기 화학식 1로 표시되는 디아민 유도체를 유효 성분으로서 사용함으로써 도열병에 대하여 우수한 방제 효과를 나타냄과 동시에 유용 작물에 대해서는 전혀 해를 끼치지 않는 살균제를 제공할 수 있다. According to the present invention, by using the diamine derivative represented by the following general formula (1) as an active ingredient, it is possible to provide a fungicide which exhibits excellent control effect against the blast bottle and does no harm to useful crops. <화학식 1> <Formula 1> 식 중, R1 내지 R7은 탄소수 1 내지 6의 알킬기 등의 특정한 치환기를 나타내고, R8은 치환될 수 있는 아릴기 또는 치환될 수 있는 헤테로아릴기를 나타낸다. In the formula, R1 to R7 represent specific substituents such as an alkyl group having 1 to 6 carbon atoms, and R8 represents an aryl group which may be substituted or a heteroaryl group which may be substituted. 디아민 유도체, 도열병, 방제 효과, 살균제 Diamine Derivatives, Blast Control, Control Effect, Fungicide

Циклогексильные производные, замещенные аминоалкиламидами

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (11) 2006 113 550 (13) A (51) ÌÏÊ C07C 311/00 (2006.01) ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2006113550/04, 13.09.2004 (71) Çà âèòåëü(è): Ô.ÕÎÔÔÌÀÍÍ-Ëß ÐÎØ Àà (CH) (30) Êîíâåíöèîííûé ïðèîðèòåò: 22.09.2003 EP 03021128.8 (43) Äàòà ïóáëèêàöèè çà âêè: 10.11.2007 Áþë. ¹ 31 (87) Ïóáëèêàöè PCT: WO 2005/028427 (31.03.2005) Àäðåñ äë ïåðåïèñêè: 101000, Ìîñêâà, Ì.Çëàòîóñòèíñêèé ïåð., 10, êâ.15, "ÅÂÐÎÌÀÐÊÏÀÒ", ïàò.ïîâ. È.À.Âåñåëèöêîé, ðåã. ¹ 11 A (54) ÖÈÊËÎÃÅÊÑÈËÜÍÛÅ ÏÐÎÈÇÂÎÄÍÛÅ, ÇÀÌÅÙÅÍÍÛÅ ÀÌÈÍÎÀËÊÈËÀÌÈÄÀÌÈ (57) Ôîðìóëà èçîáðåòåíè R U A 2 0 0 6 1 1 3 5 5 0 1. Ñîåäèíåíèå ôîðìóëû I ãäå U îçíà÷àåò àòîì êèñëîðîäà èëè íåïîäåëåííóþ ýëåêòðîííóþ ïàðó; R 1 íèçøèé àëêèë, ãèäðîêñè(íèçø.)àëêèë, öèêëîàëêèë èëè (íèçø.)àëêèë-NH-Ñ(O)-O-(íèçø.)àëêèë; R 2 íèçøèé àëêèë èëè ãèäðîêñè(íèçø.)àëêèë; R 3 âîäîðîä, íèçøèé àëêèë, ôòîð(íèçø.)àëêèë èëè öèêëîàëêèë; èëè R 2 è R 3 ñâ çûâàþòñ äðóã ñ äðóãîì ñ îáðàçîâàíèåì êîëüöà âìåñòå ñ ãðóïïîé N(CH2)k-N, ê êîòîðîé îíè ïðèñîåäèíåíû, è -R 2-R 3- ïðåäñòàâë åò íèçøèé àëêèëåí; R 4 íèçøèé àëêèë; R 5 àðèë èëè ãåòåðîàðèë; W ïðîñòóþ ñâ çü, ÑÎ, COO, CONR 6, CSO, CSNR 6, SO2 èëè SO2NR 6; R 6 îçíà÷àåò âîäîðîä èëè íèçøèé àëêèë; V ïðîñòóþ ñâ çü, íèçøèé àëêèëåí èëè (íèçø.)àëêèëåíîêñèãðóïïó; k îçíà÷àåò 2, 3 èëè 4; Ñòðàíèöà: 1 RU 2 0 0 6 1 1 3 5 5 0 (86) Çà âêà PCT: EP 2004/010197 (13.09.2004) R U (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 24.04.2006 (72) Àâòîð(û): ÀÊÊÅÐÌÀÍÍ Æàí (CH), ÝÁÈ Èîãàííåñ (CH), ÄÅÌËΠÕåíðèåòòà (DE), ÈÐÒ Æîðîæ (FR), ÌÝÐÊÈ Õàíñ-Ïåòåð (CH), ÌÎÐÀÍ Îëèâüå (CH), ÏÀÍÄÅÉ Íàðåíäðà (CH) 2 0 0 6 1 1 3 5 5 0 R U A Ñòðàíèöà: 2 2 0 0 6 1 1 3 5 5 0 ãäå R 1, R 2, R 3, R 4, R 5, U, V, W, k è m âë þòñ òàêèìè, êàê îïðåäåëåíî â ï.1, è åãî ôàðìàöåâòè÷åñêè ïðèåìëåìûå ñîëè è/èëè ôàðìàöåâòè÷åñêè ïðèåìëåìûå ñëîæíûå ýôèðû. 3. Ñîåäèíåíèå ïî ïï.1 è 2, ãäå U îçíà÷àåò íåïîäåëåííóþ ýëåêòðîííóþ ïàðó. 4. Ñîåäèíåíèå ïî ëþáîìó èç ïï.1 è 2, ãäå R 2 îçíà÷àåò ...

作为药用活性成分的6－二甲氨基甲基－1－苯基环己烷化合物

本发明公开了6-二甲氨基甲基-1-苯基环己烷化合物、其制备方法以及这些化合物在药物中的用途。

3,3-DIPHENYLPROPYLAMINDERIVATE

作为药用活性成分的6-二甲氨基甲基-1-苯基环己烷化合物

本发明公开了6-二甲氨基甲基-1-苯基环己烷化合物、其制备方法以及这些化合物在药物中的用途。

具有药理效果的1-苯基-3-二甲氨基丙烷化合物

公开了1-苯基-3-二甲氨基丙烷化合物，其制备方法和这类化合物作为药物活性成分的用途。

Amino acid amide derivative, agrohorticultural bactericide, and production process

本发明提供了包括有效量的式[I]代表的氨基酸酰胺衍生物的农业或园艺杀真菌剂。本发明的杀真菌剂是无害的化学品，且具有优良的内吸作用、残留活性和雨后存留等特性。 式中R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、Z 1 、Z 2 、Z 3 、Q、m和n的定义同说明书中定义。

페닐（알킬）카르복시산 유도체 및 디이온성페닐알킬헤테로사이클릭 유도체, 및 혈청 글루코스및／또는 혈청 지질 강하 활성을 갖는 약제로서의 그의 용도

하기 화학식 I의 화합물, 및 약제로서, 특히 혈청 글루코스 및 혈청 지질 강하제로서의 그의 용도를 개시한다: 화학식 I (상기 식에서, 각 그룹들은 명세서에서 정의한 바와 같다). 상기 약제는 당뇨병, 특히 2 형 당뇨병 및 그의 합병증, X 증후군, 다양한 형태의 인슐린 내성 및 고지혈증의 예방 및 치료에 유용하며, 부작용이 감소되었고 특히 간독성이 감소되었거나 전혀 없다. 혈청 글루코스, 혈청 지질 강하제, 당뇨병, X 증후군, 인슐린

Aryl derivatives of curcumin, demethoxycurcumin, bisdemethoxycurcumin or curcuminisoxazolide and their use as animal feed additives

本发明涉及姜黄素、去甲氧基姜黄素和二去甲氧基姜黄素的酰基衍生物和姜黄素异噁唑物作为用于改善动物机能的动物饲料组分或饲料添加剂的用途，新型的酰基衍生物本身以及含有上述衍生物的相应的动物饲料或饲料添加剂。

Nitrogen mustard prodrug having novel lipophilic protecting group and method for producing the same

(57)【要約】 本発明は、式(I)及び式(II)〔式中、X及びYは、独立に塩素、臭素、沃素、メシル基CH 3 SO 3 、又はトシル基OSO 2 フェニル（但し、場合により、フェニルがC 1-4 アルキル、ハロゲン、シアノ、又はニトロから独立に選ばれる1個、2個、3個、4個、又は5個の置換基によって置換されていてもよい）であり；R 1 及びR 2 は独立に1〜4個の任意に置換しうる置換基であり；Z 1 及びZ 2 はそれぞれ独立に-O-又は-NH-であり； R 3 は水素、t-ブチル、又はアリルであり；Z 3 はヘテロ原子を任意に含む、カルボキシエチルなどのヒドロカルビル基である〕で表される化合物、並びに該化合物の生理学的に許容しうる誘導体を提供する。該化合物は、カルボキシペプチターゼ又はニトロレダクターゼなどの酵素の働きによってナイトロジェンマスタード薬へin situで転化させることができ、癌の治療に有用である。

Isocyanate production method

Anthraquinone derivative monomer and polymer for volume Bragg grating

本公开提供了用于体布拉格光栅中的包含蒽醌衍生单体和聚合物的记录材料，所述体布拉格光栅包括但不限于用于全息术应用的体布拉格光栅。公开了用于布拉格光栅应用中的蒽醌衍生单体和聚合物的若干结构，从而产生具有更高折射率、低双折射和高透明度的材料。所公开的蒽醌衍生单体及其聚合物可用于任何体布拉格光栅材料中，包括两级聚合物材料，其中在第一步中固化基质，然后通过第二单体固化步骤写入体布拉格光栅。

1-phenyl-3-dimethylaminopropane compound, preparation method thereof and analgesic agent comprising the same

본 발명은 1-페닐-3-디에일아이노프로판 화합물, 이의 제조방법 및 약제학적 활성 성분으로서 이들 물질의 용도에 관한 것이다.

Intramolecular rearrangement-treated conjugates

본 발명은 컨쥬게이트 및 그의 약학적으로 허용되는 염, 시약, 중간체, 상기 컨쥬게이트의 합성 방법, 상기 컨쥬게이트를 포함하는 약학 조성물 및 상기 컨쥬게이트의 용도에 관한 것이다.

Niacin receptor agonists, compositions containing such compounds and methods of treatment

The present invention relates to niacin receptor agonists of formula: (I); as well as pharmaceutically acceptable salts and solvates. The compounds are useful for treating dyslipidemias, and in particular, reducing serum LDL, VLDL and triglycerides, and raising HDL levels. Pharmaceutical compositions and methods of treatment are also included.

7-and 9-carbamate, urea, thiourea, thiocarbamate and heteroaryl-amino substituted tetracycline compounds

论述取代的四环素化合物、合成方法和使用方法。也论述用于治疗四环素有关的疾病的四环素。也论述用于合成其它四环素化合物的中间体。

Compounds and compositions for delivering active agents

Carrier compounds, compositions, and dosage unit forms therefor which are useful in the delivery of active agents are provided. The present invention provides a compound having the formula: ##STR1## or a salt thereof, wherein the compound may be used in a composition or dosage unit form for delivery of at least one active agent, including a peptide, mucopolysaccharide, carbohydrate, or a lipid. Methods of administration and preparation of the compounds and compositions of the invention are provided as well, including oral administration. Further, the compositions of the invention may be prepared by mixing at least one active agent, at least one carrier compound, and, optionally, a dosing vehicle.

Compounds and compositions for delivering active agents

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Compounds and compositions for delivering active agents

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Compounds and compositions for delivering active agents

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Compounds and compositions for delivering active agents

Carrier compounds, compositions, and dosage unit forms therefor which are useful in the delivery of active agents are provided. The present invention provides a compound having the formula: ##STR1## or a salt thereof, wherein the compound may be used in a composition or dosage unit form for delivery of at least one active agent, including a peptide, mucopoly-saccharide, carbohydrate, or a lipid. Methods of administration and preparation of the compounds and compositions of the invention are provided as well, including oral administration. Further, the compositions of the invention may be prepared by mixing at least one active agent, at least one carrier compound, and, optionally, a dosing vehicle.

Compounds and compositions for delivering active agents

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Compounds and compositions for delivering active agents

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Aromatically Substituted Alkane Core Monomers and Their Polymers for Volume Bragg Gratings

本開示は、ホログラフィー用途の体積ブラッググレーティングを含むがこれに限定されない体積ブラッググレーティングにおける使用のための、芳香族置換アルカンコア誘導体化モノマー及びポリマーを含む記録材料を提供する。式Ｉを含むいくつかの構造が開示されている。ブラッググレーティング用途に使用される場合、本開示のモノマー及びポリマーは、高屈折率、低複屈折率、及び高透明性を有する材料をもたらす。本開示の誘導体化モノマー及びポリマーは、マトリックスが第１のステップで硬化され、その後モノマーの第２の硬化ステップとして体積ブラッググレーティングが書き込まれる二段階ポリマー材料を含む、任意の体積ブラッググレーティング材料において使用することができる。【選択図】なし

Amino acid amide derivatives, method of preparing fungicidal composition for agriculture or horticulture

FIELD: agriculture. SUBSTANCE: present invention describes amino acid amide derivatives of formula I: ЭзЕзстс ПЧ Го (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ” 2128 186 ' (51) МПК 13) СЛ С 07К 5/00, 5/103, 1/107, А 01 М 37/46, 47/12, 47/24 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 94046335/04, 21.04.1994 (30) Приоритет: 28.04.1993 УР 5-125455 (46) Дата публикации: 27.03.1999 (56) Ссылки: ЗИ 1836381 АЗ, 1989. КЦ 2043025 СЛ, 1989. 4$ 4284628 А, 1981. СВ 2096897 А, 1982. СВ 2106389 А, 1983. ЕР 0398072 АР, 1992. ЕР 0493683 АЛ, 1992. ЕР 0502718 А, 1992. 4Р 01301657 А, 1989. Шредер Э., Любке К. Пептиды. - М.: М ир, 1967, ч.1, с. 116. Шевченко Л.И. и др. Физиологически активные вещества. - Киев: 1985, М 17, с.55 - 57. (85) Дата перевода заявки РСТ на национальную фазу: 27.12.94 (86) Заявка РСТ: УР 9400708 (27.04.94) (87) Публикация РСТ: М/О 94/25432 (10.11.94) (98) Адрес для переписки: 103735, Москва, ул.Ильинка, 5/2, Союзпатент (71) Заявитель: Кумиай Кемикал Индастри Ко., Лтд. (Р), Ихара Кемикал Индастри Ко., Лтд. (УР) (72) Изобретатель: Масару Сибата (/Р), Казухико Сугияма (.Р), Норихиса Енекура (УР), Дзунетсу Сакаи (/Р), Есиюки Кодзима (УР), Сигеру Хаяси (Р) (73) Патентообладатель: Кумиай Кемикал Индастри Ко., Лтд. (Р), Ихара Кемикал Индастри Ко., Лтд. (4Р) (54) ПРОИЗВОДНЫЕ АМИДОВ АМИНОКИСЛОТ, СПОСОБ ПОЛУЧЕНИЯ, ФУНГИЦИДНАЯ КОМПОЗИЦИЯ ДЛЯ СЕЛЬСКОГО ХОЗЯЙСТВА И САДОВОДСТВА (57) Реферат: Производное амида аминокислоты формулы |, 2. 3 _5 т 2; о в = Е гаи | | з | в 2 е-мн-сн-с-мн-с-сс> 7 -6С> = ст» м п г. Га Ц: Ц: Е Е Е Е в которой радикалы принимают значения, указанные в п. 1 формулы изобретения, проявляют широкий спектр противогрибковой активности, особенно против — Ложной мучнистой росы огурцов, против ложной мучнистой росы винограда и фитофтороза томата. 4 с. и 7 з.п. ф-лы, 20 табл. 2128186 С1 КО ЭзЕзстс ПЧ Го (19) КУЗЗАМ АСЕМСУ ГОК РАТЕМТ$ АМО ТКАОЕМАКК$ 12) АВЗТКАСТ ОЕ 1МУЕМТОМ ВИ” 2128 186 ' (51) 1пЕ. С1.6 13) СЛ 01 М ...

Phenyl and pyridyl lta4h modulators

Leukotrfene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and inflammatory conditions.