Method for preparing a poly(ether sulfonimide or -amide) copolymer using cyclic oligomers

Disclosed is a method for preparing a poly(ethersulfonimide or ethersulfonamide) copolymer using cyclic oligomers, and more particularly, to a method for preparing a poly(ethersulfonimide or ethersulfonamide) copolymer by preparing a cyclic ether sulfone oligomer and a cyclic imide or amide oligomer and subjecting the cyclic ether sulfone oligomer and the cyclic imide or amide oligomer to ring-opening copolymerization in the presence of an alkali metal fluoride catalyst.

Bridged Macrocyclic Module Compositions

This invention is related to the fields of organic chemistry and nanotechnology. In particular, it relates to materials and methods for the preparation of organic synthons and bridged macrocyclic module components. The bridge macrocyclic module compounds may be used to prepare macrocyclic module compositions such as nanofilms, which may be useful for filtration. 2. The compound of claim 1 , wherein the two or more termini of said bridge moiety are coupled to synthons.3. The compound of claim 1 , wherein the two or more termini of said bridge moiety are coupled to L moieties claim 1 , with the proviso that said L moieties to which the termini are coupled are not direct bonds.4. The compound of claim 1 , wherein n′ is from 4 to 24.5. The compound of claim 1 , wherein n′ is from 6 to 12.98. The compound of - claims 6 , wherein each Qis the same synthon.108. The compound of - claims 6 , wherein each Qis the same synthon.118. The compound of - claims 6 , wherein each Qis the same synthon.158. The compound of - claims 6 , wherein each L between the synthons are the same.168. The compound of - claims 6 , wherein each L between the bridge moiety and the synthons are the same.17. The compound of claim 1 , wherein the synthons are cyclic synthons.18. The compound of claim 1 , wherein the synthons are acyclic synthons.19. The compound of claim 1 , wherein each L is a direct bond.21. The compound of claim 1 , wherein the bridge moiety further comprises a surface attachment group.22. The compound of claim 1 , wherein the bridge moiety further comprises a lipophilic group.23. The compound of claim 1 , wherein the bridge moiety comprises a functional group for coupling the compound to at least a second bridged macrocyclic module compound.24. The compound of claim 1 , wherein the bridge moiety comprises a polymerization center.26. A nanofilm comprising a plurality of bridged macrocyclic modules of .27. The nanofilm of claim 26 , wherein the thickness of the nanofilm composition is ...

APOPTOSIS PROMOTERS

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member. 19-. (canceled)10. A compound , or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(2,4-dimenthyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;4-(((1R)-3-(bis(2-methoxyethyl)amino)-1 ...

Cyclic amides

The invention relates to a compound of formula (I) wherein A, B, D and R 1 to R 6 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIA

The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes. 2. A compound of the formula I as claimed in claim 1 , where{'sub': '2', 'X is —C(O)— or —SO—,'}{'sub': 0', '4, 'U is oxygen atom, sulfur atom, NH, —C(O)—NH— or —(C-C)-alkylene-,'}{'sub': 0', '4, 'A is oxygen atom, sulfur atom, NH, —C(O)—NH— or —(C-C)-alkylene-,'}V is{'sub': 2', '9, '1) —(C-C)-alkylene- or'}{'sub': 3', '9, '2) —(C-C)-alkenylene-,'}{'sub': 1', '2, 'D is —(C-C)-alkylene-,'}Y is1) covalent bond,{'sub': 3', '12, '2) —(C-C)-cycloalkyl, where cycloalkyl is substituted independently of one another once, twice or three times by R15,'}{'sub': 6', '14, '3) —(C-C)-aryl, where aryl is unsubstituted or substituted independently of one another once, twice or three times by R15, or'}4) Het, where Het means a 4- to 15-membered heterocyclic ring system having 4 to 15 ring atoms, which are present in one, two or three ring systems which are connected together, and which comprise, depending on the ring size, one, two, three or four identical or different heteroatoms from the series oxygen, nitrogen or sulfur, and{'sub': 1', '3', '2', '3', '3, 'in which Het is unsubstituted or substituted independently of one another once, twice or three times by a —(C-C)-alkyl, halogen, —NH, —CFor —O—CF,'}R1 is1) hydrogen atom,{'sub': 1', '6, '2) —(C-C)-alkyl,'}{'sub': 1', '6, '3) —(C-C)-alkyl-OH,'}{'sub': 0', '4', '3', '6, '4)-(C-C)-alkyl-(C-C)-cycloalkyl,'}{'sub': 1', '10, '5) —(C-C)-alkyl-O—C(O)—O—R2,'}{'sub': 2', 'r', '6', '14, '6) —(CH)—(C-C)-aryl, in which aryl is unsubstituted or substituted independently of one another once, twice or three times by R15, and r is the integer zero, 1, 2 or 3, or'}{'sub': 2', 's, '7) —(CH)-Het, ...

Histone Deacetylase Inhibitors for Enhancing Activity of Antifungal Agents

The present invention relates to compositions and methods to selectively treat fungal infection. More particularly, the invention relates to compounds, compositions thereof, and methods for selectively enhancing fungal sensitivity to antifungal compounds. The compositions of the invention are comprised of a combination of a histone deacetylase inhibitor, or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt, agricultural formulation, prodrug or complex thereof, and an antifungal agent, the histone deacetylase inhibitor being a compound of Formula (I): 119.-. (canceled)21. The inhibitor of claim 20 , where B is phenyl.24. The inhibitor of claim 20 , where the butyl group is substituted at one or more positions with one or two methyl claim 20 , ethyl claim 20 , fluoro claim 20 , chloro claim 20 , bromo claim 20 , or hydroxyl groups claim 20 , or one oxo claim 20 , amino claim 20 , or oxime group.25. The inhibitor of claim 24 , where the butyl group is substituted at one position with one methyl claim 24 , ethyl claim 24 , fluoro claim 24 , chloro claim 24 , bromo claim 24 , oxo claim 24 , amino claim 24 , oxime or hydroxyl group.26. The inhibitor of claim 24 , where the butyl group is substituted at the same position with two methyl claim 24 , ethyl claim 24 , fluoro claim 24 , chloro claim 24 , bromo or hydroxyl groups.27. The inhibitor of claim 20 , where the butyl group is unsubstituted.28. The inhibitor of claim 20 , where Rand Rare independently hydrogen or methyl.29. (canceled)30. (canceled)32. (canceled)34. A histone deacetylase inhibitor selected from the group consisting of:N-hydroxy-2-(2-(4-phenylbutyl)thiazol-4-yl)acetamide,N-hydroxy-2-(2-(4-phenylbutyl)thiazol-5-yl)acetamide,2-(4-(4-(2,4-difluorophenyl)butyl)phenyl)-N-hydroxyacetamide,N-hydroxy-2-(4-(4-p-tolylbutyl)phenyl)acetamide,2-(4-(4-(biphenyl-4-yl)butyl)phenyl)-N-hydroxyacetamide,N-hydroxy-2-(4-(4-(1-methyl-1H-indol-5-yl)butyl)phenyl)acetamide,2,2′-(4,4′-(butane-1,4-diyl)bis(4,1- ...

SONIC HEDGEHOG MODULATORS

Sonic Hedgehog modulators and methods of use thereof are provided for. 2169-. (canceled)171177-. (canceled)179181-. (canceled)183185-. (canceled)187192-. (canceled)194223-. (canceled)225226-. (canceled)228233-. (canceled)235249-. (canceled)251258-. (canceled)260269-. (canceled)270. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.271. A method of treating a Sonic Hedgehog associated disorder in a subject comprising administering to said subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , such that said subject is treated for said disorder.272277-. (canceled)278. A method of inhibiting Sonic Hedgehog protein induced transcription in cells by contacting the cells with an effective amount of a compound of claim 1 , such that said transcription is inhibited.279. (canceled)280. A pharmaceutical composition comprising a compound of claim 193 , and a pharmaceutically acceptable carrier.281. A method of treating a Sonic Hedgehog associated disorder in a subject comprising administering to said subject an effective amount of a compound of claim 193 , or a pharmaceutically acceptable salt thereof claim 193 , such that said subject is treated for said disorder.282. A method of inhibiting Sonic Hedgehog protein induced transcription in cells by contacting the cells with an effective amount of a compound of claim 193 , such that said transcription is inhibited.283. A pharmaceutical composition comprising a compound of claim 234 , and a pharmaceutically acceptable carrier.284. A method of treating a Sonic Hedgehog associated disorder in a subject comprising administering to said subject an effective amount of a compound of claim 234 , or a pharmaceutically acceptable salt thereof claim 234 , such that said subject is treated for said disorder.285. A method of inhibiting Sonic Hedgehog protein induced transcription in cells by contacting the cells with an effective ...

AGONISTS OF EPHA AND THEIR USES

A method of treating cancer in a subject includes administering to the subject a therapeutically effective amount of a small molecule agonist of EphA2 receptor protein, the small molecule having a general formula: A-L-X-Z (I). 11. The method of claim 1 , wherein the small molecule agonist of EphA2 receptor protein is not doxazosin.12. The method of claim 1 , the small molecule agonist of EphA2 receptor having a lower α-adrenoreceptor binding affinity than doxazosin.13. The method of claim 1 , wherein the therapeutically effective amount of a small molecule agonist of EphA2 receptor is the amount effective to inhibit tumor growth associated with EphA2 tumorgenesis in the subject.14. The method of claim 1 , wherein the therapeutically effective amount of a small molecule agonist of EphA2 receptor is the amount effective to activate and internalize EphA2 receptors in cancer cells of the subject.15. The method of claim 1 , the cancer characterized by the overexpression of EphA2 in cancer cells of the subject.16. The method of claim 15 , the cancer selected from the group consisting of breast cancer claim 15 , prostate cancer claim 15 , carcinoma claim 15 , and glioma. This application claims priority from U.S. Provisional Application No. 62/528,194, filed Jul. 3, 2017, the subject matter of which is incorporated herein by reference in its entirety.As a member of the erythropoietin-producing hepatocellular (Eph) subfamily of receptor tyrosine kinases (RTKs), EphA2 was originally called epithelial cell kinase, or Eck, due to its widespread expression in epithelial cells in vitro and in vivo. Subsequent studies revealed that EphA2 was overexpressed in human cancers, and that overexpression was correlated with malignant progression and poor prognosis.A large number of studies have demonstrated that EphA2 overexpression and activation promote tumorigenesis, suggesting a potential role as an oncogene. Overexpression of EphA2 in breast epithelial cells induced morphological ...

Creatine prodrugs, compositions and methods of use thereof

The present disclosure provides creatine prodrug analogs and their compositions useful for the treatment of creatine deficiencies.

MACROCYCLIC COMPOUNDS FOR MODULATING IL-17

The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders. 2. The compound of claim 1 , wherein R′ is selected from —O— claim 1 , —N(H)— and —N(CH)—.3. The compound of claim 1 , wherein Ris selected from *—CH(R)—Z— and *—C(H)(R)—X—C(H)(R)—N(R)—C(O)—C(H)(R)—(CH)— claim 1 , wherein:{'sub': 2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3, 'X is selected from —CH—O—CH—, —CH—N(H)—CH—, —CH—N(CH)—CH—, —CH—, —(CH)—, and —(CH)—;'}{'sub': 2', '8', '2', '8', '2', '8', '3, 'Z is selected from C-Calkylene, C-Calkenylene, or C-Calkynylene, wherein up to 2 methylene units in Z are optionally and independently replaced with —O—, —N(H)— or —N(CH)—;'}{'sup': 10', '10, 'each Ris independently selected from hydrogen and —(R)—COOH, wherein at least one Ris hydrogen;'}{'sup': '11', 'sub': 2', '3', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '4', '2, 'Ris selected from hydrogen, (S)—CHOH, (S)—CH, (S)—C(CH), (S)-benzyl, (R)-benzyl, (S)—CH-pyridinyl, (S)-cyclohexyl, (S)—CH-cyclohexyl, (S)—(CH)—COOH, (S)—(CH)—C(O)NH, and (S)—(CH)—NH;'}{'sup': '12', 'sub': '3', 'Ris selected from hydrogen and —CH; and'}{'sup': 2', '1, '“*” represents a terminus of Rbound to R.'}4. The compound of claim 1 , wherein Ris selected from *—(CH)— claim 1 , *—CH(COOH)—(CH)— claim 1 , *—(CH)—O—(CH)— claim 1 , *—(CH)—O—(CH)—O—(CH)— claim 1 , *—(CH)—NH—(CH)— claim 1 , *—(CH)—N(CH)—(CH)— claim 1 , *—CH—C≡C—(CH) claim 1 , and *—CH—CH═CH—(CH).7. The compound of claim 1 , wherein Ris selected from —(CH)— and —CH-(1 claim 1 ,4-phenylene)-† claim 1 , wherein “†” represents a portion of Rbound to N(R).8. The compound of claim 1 , wherein Ris —CH-(1 claim 1 ,4-phenylene)-†; and the stereochemistry of the carbon adjacent to Ris (5).9. The compound of ...

CYCLIC CARBONATE MONOMERS AND RING OPENED POLYCARBONATES THEREFROM

Eight-membered ring cyclic carbonates having an oxygen or an acylated nitrogen at position 6 were prepared by reaction of precursor diols with ethyl chloroformate. The cyclic carbonates undergo organocatalyzed ring opening polymerization. In one instance, the initial polymer formed comprises a carbonate repeat unit having a Boc-protected nitrogen in the polymer backbone. Deprotecting the nitrogen with acid forms a cationic carbonate repeat unit having a positive charged secondary ammonium nitrogen in the polymer backbone. 2. The compound of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , iso-propyl claim 1 , butyl claim 1 , sec-butyl claim 1 , t-butyl claim 1 , phenyl claim 1 , benzyl claim 1 , and allyl.3. The compound of claim 1 , wherein each R′ is selected from the group consisting of t-butyl claim 1 , ethyl claim 1 , and allyl.6. The method of claim 5 , wherein the solvent is tetrahydrofuran.7. The method of claim 5 , wherein the amine base is triethylamine.11. The method of claim 10 , wherein Ris selected from the group consisting of methyl claim 10 , ethyl claim 10 , n-propyl claim 10 , iso-propyl claim 10 , butyl claim 10 , sec-butyl claim 10 , t-butyl claim 10 , phenyl claim 10 , benzyl claim 10 , and allyl.12. The method of claim 10 , wherein R′ is selected from the group consisting of t-butyl claim 10 , ethyl claim 10 , and allyl.13. The method of claim 10 , wherein the polycarbonate comprises a residue of the initiator.18. The method of claim 17 , wherein the acid is trifluoroacetic acid.21. The compound of claim 20 , wherein Ris selected from the group consisting of methyl claim 20 , ethyl claim 20 , n-propyl claim 20 , iso-propyl claim 20 , butyl claim 20 , sec-butyl claim 20 , t-butyl claim 20 , phenyl claim 20 , benzyl claim 20 , and allyl.24. The polymer of claim 23 , wherein Ris selected from the group consisting of methyl claim 23 , ethyl claim 23 , n-propyl claim 23 , iso-propyl ...

COMPOUNDS AND METHODS FOR TREATING FIBROSIS OR CANCER

Provided herein, inter alia, are methods and compounds for treating a pulmonary disease, fibrosis, or cancer. 3. The compound of claim 1 , wherein Ris —NH claim 1 , —OH claim 1 , or substituted or unsubstituted heteroalkyl.4. (canceled)5. The compound of claim 1 , wherein Ris —NH claim 1 , —OH claim 1 , or substituted or unsubstituted heteroalkyl.6. (canceled)7. The compound of claim 1 , wherein Ris —NH claim 1 , —OH claim 1 , or substituted or unsubstituted heteroalkyl.8. (canceled)9. The compound of claim 1 , wherein Ris —NH claim 1 , —OH claim 1 , or substituted or unsubstituted heteroalkyl.10. (canceled)11. The compound of claim 1 , wherein Ris —NH claim 1 , —OH claim 1 , or substituted or unsubstituted heteroalkyl.12. (canceled)13. The compound of claim 1 , wherein Ris —NH claim 1 , —OH claim 1 , or substituted or unsubstituted heteroalkyl.14. (canceled)17. (canceled)18. (canceled)19. (canceled)20. The compound of claim 1 , wherein Ris independently —COOR claim 1 , —NRC(O)OR claim 1 , or —C(O)R.2128.-. (canceled)29. The compound of claim 1 , wherein Ris independently hydrogen.30. The compound of claim 1 , wherein Ris independently hydrogen.31. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.32. A method of reducing the level of activity of zinc finger protein Snail1 in a subject claim 1 , said method comprising administering an effective amount of a compound of to the subject.33. A method of reducing the level of activity of Lysyl oxidase homolog 2 (LOXL2) in a subject claim 1 , said method comprising administering an effective amount of a compound of to the subject.34. A method of inhibiting collagen cross-linking in a subject claim 1 , said method comprising administering an effective amount of a compound of to the subject.35. A method of treating fibrosis claim 1 , said method comprising administering to a subject in need thereof an effective amount of a compound of .36. (canceled)37. (canceled)38. A method ...

Process for preparing fluoxastrobin

The disclosure includes a process for preparing fluoxostrobin which includes: (i) reacting benzofuran-3(2H)-one O-methyl oxime (10) with an alkyl nitrite in the presence of an acid to form (3E)-2,3-benzofuran-dione O 3 -methyl dioxime (11A) as a predominant isomer; (ii) reacting (3E)-2,3-benzofuran-dione O 3 -methyl dioxime (11A) with 2-haloethanol to form (3E)-benzofuran-2,3-dione O 2 -(2-hydroxyethyl) O 3 -methyl dioxime (12A); and (iii) reacting (3E)-benzofuran-2,3-dione O 2 -(2-hydroxyethyl) O 3 -methyl dioxime (12A) with a base to form (E)-(5,6-dihydro-1,4,2-dioxazin-3-yl)(2-hydroxyphenyl)methanone O-methyl oxime (13) (iv) reacting a 4,6-di-halo-5-fluoro-pyrimidine (5), wherein X 1 is halogen, with (E)-(5,6-dihydro-1,4,2-dioxazin-3-yl)(2-hydroxyphenyl)methanone O-methyl oxime (13), in the presence of a solvent and optionally in the presence of a base, to form an (E)-(2-((6-halo-5-fluoropyrimidin-4-yl)oxy)phenyl)(5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyl oxime (14): (v) reacting the (E)-(2-((6-halo-5-fluoropyrimidin-4-yl)oxy)phenyl)(5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyl oxime (14) with 2-chlorophenol, in the presence of a solvent and optionally in the presence of a base, to form fluoxastrobin:

MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIA

The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes. 2. (canceled)3: A compound of the formula (I) claim 1 , a stereoisomer thereof claim 1 , or a physiologically tolerated salt of any of the foregoing claim 1 , as claimed in claim 1 , wherein{'sub': 5', '8', '3', '6, 'V is —(C-C)-alkylene- or —(C-C)-alkenylene-;'}{'sub': 6', '14, 'Y is —(C-C)-aryl, wherein said aryl is selected from the group consisting of phenyl, naphthyl, anthryl and fluorenyl, and wherein said aryl is unsubstituted or substituted independently of one another once, twice or three times by R15;'}R1 is1) a hydrogen atom, or{'sub': 1', '4, '2) —(C-C)-alkyl;'}R3 is{'sub': 2', '6', '2, '1) —(C-C)-alkylene-NH, wherein said alkylene is unsubstituted or substituted once, twice, three or four times by halogen,'}{'sub': 1', '4', '2', '1', '4', '2, '2) —(C-C)-alkylene-SO—(C-C)-alkylene-NH, or'}{'sub': 0', '4', '2, '3) —(C-C)-alkylene-Het, wherein said Het is as defined above and is substituted by —NHand once, twice or three times by R15;'}R6 is1) a hydrogen atom,{'sub': 1', '6, '2) —(C-C)-alkyl, wherein said alkyl is unsubstituted or substituted independently of one another once, twice or three times by R16,'}{'sub': 1', '6, '3) —O—(C-C)-alkyl, wherein said alkyl is unsubstituted or substituted independently of one another once, twice or three times by R16,'}{'sub': 0', '4, '4) —(C-C)-alkylene-Het, wherein said Het is as defined above, wherein said alkylene and Het are unsubstituted or substituted independently of one another once, twice or three times by R16,'}{'sub': 0', '4, '5) —(C-C)-alkylene-aryl, wherein said alkylene and aryl are unsubstituted or substituted independently of one another once, twice or ...

Reactive mesogen and liquid crystal composition including the same

Provided are a reactive mesogen that may improve display quality of a liquid crystal display, and a liquid crystal composition including the same. The reactive mesogen is represented by the following Formula: where A 1 , A 2 , and A 3 are each independently a substituted or unsubstituted divalent hydrocarbon ring, or a substituted or unsubstituted divalent heterocycle, L 1 and L 2 are each independently a direct linkage, —O—, —S—, —CO—, —COO—, —OCOO—, —O(CH 2 ) k1 —, —S(CH 2 ) k1 —, —O(CF 2 ) k1 —, —S(CF 2 ) k1 —, —(CH 2 ) k1 —, —CF 2 CH 2 —, —(CF 2 ) k1 —, —CH═CH—, —CF═CF—, —C≡C—, —CH═CH—COO—, or —(CH 2 ) k1 —COO—(CH 2 ) k2 —O—, Z 1 and Z 2 are each independently a direct linkage, —O—, —S—, —CO—, —COO—, —OCOO—, —O(CH 2 ) m1 —, —S(CH 2 ) m1 —, —O(CF 2 ) m1 —, —S(CF 2 ) m1 —, —(CH 2 ) m1 —, —CF 2 CH 2 —, —(CF 2 ) m1 —, —CH═CH—, —CF═CF—, —C≡C—, —CH═CH—COO—, —(CH 2 ) m1 —COO—, —(CH 2 ) m1 —COO—(CH 2 ) m2 —O—, —CH—(S p —Pa)—, —CH 2 CH—(S p —Pa)—, or —(CH—(S p —Pa)—CH—(S p —Pa))—, Pa is a polymerizable group, B is an unsubstituted heterocycle, a substituted or unsubstituted crown ether group, or wherein T 1 and T 2 are each independently —OH, —CH 3 , —CF 3 , —CHF 2 , —CH 2 F, —CH 2 Br, —CHBr 2 , —CHCl 2 , or —CH 2 Cl.

Simplified Structural Mimetics of AIPS as Quorum Sensing Inhibitors

Compounds that regulate quorum sensing in Staphylococcal bacteria and in particular in Staphylococcus aureus are provided. Compounds are described in formulas I, II, III, IV, V and VI herein. One or more compounds herein can be employed to inhibit QS and to thus inhibit virulence in Staphylococcus bacteria and in particular in Staphylococcus aureus. Compounds herein and pharmaceutical compositions containing one or more of these compounds are useful, for example, in treating infections of Staphylococcus bacteria and in particular of Staphylococcus aureus. Methods for treating such bacterial infections are provided.

PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF PIMAVANSERIN

The present disclosure relates to novel, safe and efficient processes for the synthesis of Pimavanserin and salts thereof, as well as novel intermediates that can be used in these processes. 121-. (canceled)25. The compound of formula (XVIII) or (XIX) of claim 22 , wherein Ris 2-methylpropan-oxy.27. The process of claim 26 , wherein Ris an isobutoxy group.34. The process of claim 33 , wherein the compound of formula (V) is prepared by reacting 4-fluorobenzylamine with 1-methylpiperidine-2-one.36. The process of claim 35 , wherein the compound of formula (V) by reacting 4-fluorobenzylamine with 1-methylpiperidine-2-one.38. The process of claim 37 , wherein the compound of formula (V) by reacting 4-fluorobenzylamine with 1-methylpiperidine-2-one. This application claims the benefit of U.S. Provisional Application Nos. 62/126,840, filed Mar. 2, 2015; 62/161,421, filed May 14, 2015; 62/187,668, filed Jul. 1, 2015; 62/188,992, filed Jul. 6, 2015; 62/198,218, filed Jul. 29, 2015; and 62/270,310, filed Dec. 21, 2015, the entireties of which are incorporated by reference herein.The present disclosure relates to novel, safe and efficient processes for the synthesis of Pimavanserin and salts thereof, as well as novel intermediates that can be used in these processes.Pimavanserin tartrate, 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1-methylpiperidin-4-yl)urea L-hemi-tartrate, has the following chemical structure:Pimavanserin tartrate was developed by Acadia Pharmaceuticals and was approved under the trade name NUPLAZID® for use in patients with Parkinson's disease psychosis.Pimavanserin free base and its synthesis are disclosed in U.S. Pat. No. 7,601,740 (referred to herein as US '740 or the '740 patent) and U.S. Pat. No. 7,790,899 (referred to herein as US '899 or the '899 patent). US '740 discloses the synthesis of Pimavanserin free base (also referred to herein as “Compound A”), which includes O-alkylation followed by ester hydrolysis, and then in situ azidation. This ...

Macrocyclic ghrelin receptor modulators and methods of using the same

The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone sceretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

SONIC HEDGEHOG MODULATORS

Sonic Hedgehog modulators and methods of use thereof are provided for. 2279-. (canceled) This application is a continuation application of U.S. patent application Ser. No. 13/781,000, filed Feb. 28, 2013; which is a continuation application of U.S. patent application Ser. No. 13/553,612, filed Jul. 19, 2012, which is a continuation application of U.S. patent application Ser. No. 13/309,690, filed Dec. 2, 2011, which is a continuation of U.S. patent application Ser. No. 13/008,214, filed Jan. 18, 2011, which is a continuation of U.S. patent application Ser. No. 12/764,855, filed Apr. 21, 2010; which claims benefit of U.S. Provisional Patent Application No. 61/171,245, filed Apr. 21, 2009. The contents the foregoing applications are hereby incorporated by reference in their entirety.The present invention relates to macrocyclic small molecule modulators of the Sonic Hedgehog signaling pathway, syntheses thereof, and intermediates thereto. The invention also provides pharmaceutical compositions comprising compounds of the present invention and methods of using said compounds in the treatment of proliferative diseases (e.g., benign neoplasm, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and developmental disorders.The Hedgehog (Hh) pathway has been implicated in many developmental processes, including organogenesis in most animals (Ingham, P. W., McMahon, A. P. . 15, 3059-3087, 2001; Frank-Kamenetsky, M., et al. . 10, 1-19, 2002). First identified in in 1980, three mammalian homologues of Hh proteins, Sonic Hedgehog (Shh), Desert Hedgehog, (Dhh) and Indian Hedgehog (Ihh), are all key regulators of anterior/posterior patterning in limb development, the induction of polarity in the central nervous system, and the differentiation of numerous cell types (Nusslein-Volhard, C., Wieschaus, E. 287, 795-801, 1980); Weitzman, J. B. . 7, 1-5, 2002; Pepinsky, R. B. et al. 275, 10995-11001, 2000; Stecca, B., Altaba, A. R. . 9, 1-4, 2002). Shh is the most ...

THERAPEUTIC CYCLIC COMPOUNDS AS IMMUNOMODULATORS

The present invention relates to cyclic compounds of formula (I) and their use to inhibit the programmed cell death 1 (PD-1) signaling pathway and/or for treatment of disorders by inhibiting an immunosuppressive signal induced by PD-1, PD-L1 or PD-L2. 5. The compound according to claim 1 , wherein claim 1 ,{'sub': '1', 'Ris side chain of Ser, Tyr, Ile, Asp, Lys, Phe, Asn, Gln, Glu, Trp, His, Arg, Val or Thr;'}{'sub': '2', 'Ris side chain of Asp, Asn, Ile, Lys, Phe, Ser, Thr, Val or Glu;'}{'sub': 1', '2, 'R′ and R′ are each hydrogen;'}{'sub': 3', '4', '4', '5, 'R, R, R′ and Rindependently are hydrogen;'}{'sub': '6', 'Ris side chain of Ser, Leu, Tyr, Lys, Asp, Asn, Glu, Gln, Val or Thr;'}{'sub': a', 'a, 'both Rand R′ together represent an oxo (═O) group;'}{'sub': b', 'b, 'both Rand R′ together represent an oxo (═O) group;'}{'sub': 2', 'm', '2', '2', 'n, 'L is —C(O)—(CH)—(X—CH—CH)—NH—;'}X is O;m is an integer from 0 to 3;n, independently for each occurrence, is an integer from 2 to 20; or a pharmaceutically acceptable salt or a stereoisomer thereof.6. The compound according to any one of to claim 1 , wherein Ris (C-C)alkyl claim 1 , (C-C)alkenyl or (C-C)alkynyl; wherein (C-C)alkyl claim 1 , (C-C)alkenyl and (C-C)alkynyl are optionally substituted by one or more substituents selected from hydroxy claim 1 , amino claim 1 , amido claim 1 , alkylamino claim 1 , acylamino claim 1 , —(CH)—COOH claim 1 , —(CH)—COO-alkyl claim 1 , cycloalkyl claim 1 , heterocyclyl claim 1 , heteroaryl claim 1 , guanidino claim 1 , (cycloalkyl)alkyl claim 1 , (heterocyclyl)alkyl claim 1 , (heteroaryl)alkyl and (alkyl)—S—.7. The compound according to the claim 6 , wherein Ris (C-C)alkyl wherein the said (C-C)alkyl is optionally substituted by cycloalkyl or —S—(alkyl).8. The compound according to any one of and claim 6 , wherein Rand R′ together with the carbon atom to which they are attached form cycloalkyl ring; the said cycloalkyl is cyclopentyl or cyclohexyl.9. The compound according to any ...

CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS

The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases. 4. A compound according to claim 1 , wherein {'sub': B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'c', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'c', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C', 'B', 'C, 'A1-A1; A1-A4; A1-A6; A1-A8; A1-A9; A1-A11; A1-A13; A1-A19; A1-A22; A1-A24; A1-A49; A1-A51; A2-A4; A2-A51; A4-A1; A4-A4; A4-A6; A4-A19; A4-A22; A4-A24; A4-A49; A4-A51; A4-A59; A5-A51; A5-A59; A6-A1; A6-A4; A6-A8; A6-A9; A6-A11; A6-A13; A6-A16; A6-A18; A6-A19; ...

CYCLIC CARBODIIMIDE COMPOUND, POLYESTER FILM, BACK SHEET FOR SOLAR CELL MODULE, AND SOLAR CELL MODULE

A polyester film including a cyclic carbodiimide compound represented by the following Formula (O-1) has good film thickness uniformity without increase in viscosity. Rand Rrepresent an alkyl group, an aryl group, or an alkoxy group; Rto Rand Rto Rrepresent a hydrogen atom, an alkyl group, an aryl group, or an alkoxy group; Xand Xrepresent a single bond, —O—, —CO—, —S—, —SO—, —NH—, or —CH—; and Lrepresents a divalent linking group. 2. The cyclic carbodiimide compound according to claim 1 , wherein both Rand Rin Formula (O-1) are hydrogen atoms.3. The cyclic carbodiimide compound according to claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rin Formulas (O-1) and (O-2) independently represents a secondary or tertiary alkyl group claim 1 , or an aryl group.5. The polyester film according to claim 4 , wherein both Rand Rin Formula (O-1) are hydrogen atoms.6. The polyester film according to claim 4 , wherein each of R claim 4 , R claim 4 , R claim 4 , R claim 4 , Rand Rin Formulas (O-1) and (O-2) independently represents a secondary or tertiary alkyl group claim 4 , or an aryl group.7. The polyester film according to claim 4 , comprising the cyclic carbodiimide compound in an amount of 0.05% by mass to 5% by mass relative to 100% by mass of the polyester.8. The polyester film according to claim 4 , wherein a component derived from carboxylic acid in the polyester is a component derived from an aromatic dibasic acid or its derivative for forming an ester.9. The polyester film according to which is biaxially oriented. This application is a continuation application of International Application No. PCT/JP2013/062184, filed Apr. 25, 2013, which in turn claims the benefit of priority from Japanese Application No. 2012-113227, filed on May 17, 2012, and Japanese Application No. 2012-180258, filed on Aug. 15, 2012, the disclosures of which Applications are incorporated by reference herein in their entirety.1. Field of the InventionThe present ...

Cyclic Peptidomimetic Compounds as Immunomodulators

The present invention relates to cyclic peptidomimetic compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The invention also relates to derivatives of the therapeutic agents. The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them. 6. The compound according to claim 1 , wherein Ris Calkyl; or R′ is Calkyl.8. A pharmaceutical composition comprising at least one compound according to or a pharmaceutically acceptable salt or a stereoisomer thereof claim 1 , and a pharmaceutically acceptable carrier or excipient.9. The pharmaceutical composition according to further comprising at least one of an anticancer agent claim 8 , chemotherapy agent claim 8 , or antiproliferative compound.10. A method of modulating an immune response mediated by PD-1 signaling pathway in a subject claim 1 , comprising administering to the subject a therapeutically effective amount of a compound according to .11. A method of inhibiting growth of tumour cells and/or metastasis in a subject claim 1 , comprising administering to the subject a therapeutically effective amount of a compound according to .12. The method of claim 11 , wherein the tumour cells are from a cancer selected from the group consisting of breast cancer claim 11 , colon cancer claim 11 , lung cancer claim 11 , melanoma claim 11 , prostate cancer and renal cancer.13. The method of claim 11 , wherein the tumour cells are from a cancer selected from the group consisting of bone cancer claim 11 , cancer of the head or neck claim 11 , pancreatic cancer claim 11 , skin cancer claim 11 , cutaneous or intraocular malignant endometrium claim 11 , carcinoma of the cervix claim 11 , carcinoma of the vagina claim 11 , carcinoma of the vulva claim 11 , Hogkin's Disease claim 11 , non-Hodgkin's ...

1,3,6-dioxazocan-2-ones and antimicrobial cationic polycarbonates therefrom

Eight-membered ring cyclic carbonates comprising a ring nitrogen at position 6 (1,3,6-dioxazocan-2-ones) were prepared by reaction of precursor diols with active carbonates. The ring nitrogen is linked to a pendant group Y′ via a methylene linking group. The cyclic carbonates undergo organocatalyzed ring opening polymerization to form an initial polycarbonate comprising a backbone tertiary amine group. Quaternization of the initial polycarbonates forms cationic polycarbonates comprising a positive-charged backbone quaternary nitrogen. The cationic polycarbonates can be potent antimicrobial agents.

ANTHELMINTIC DEPSIPEPTIDE COMPOUNDS

The present invention provides cyclic depsipeptide compounds of formula (I) and compositions comprising the compounds that are effective against parasites that harm animals, including humans. The compounds and compositions may be used for combating parasites in or on animals including mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in animals, including birds and mammals. 2. The anthelmintic cyclic depsipeptide of claim 1 , wherein{'sup': 1', '2', '1′', '2′, 'sub': 1', '3', '1', '3', '1', '3', '1', '3', '1', '3, '(e) Rand/or Rare each independently C-Calkyl or C-Chaloalkyl, wherein the C-Calkyl or C-Chaloalkyl is substituted by a 3- to 8-membered non-aromatic carbocyclic ring; wherein said 3- to 8-membered non-aromatic carbocyclic ring(s) may be further independently substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and R and/or R are independently hydrogen or C-Calkyl; or'}{'sup': 1', '1′', '2', '2′, 'Rand R together and/or Rand R together independently form a 2-6-membered carbon chain to form a ring; and'}{'sup': 3', '3′', '4', '4′, 'sub': 1', '8, 'R, R, Rand R are each independently hydrogen or C-Calkyl, optionally substituted by one or more halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkyl sulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino or dialkylamino; or'}{'sup': 1', '3', '1′', '3′, 'sub': 1', '3', '1', '3', '1', '3', '1', '3', '1', '3, '(f) Rand/or Rare each independently C-Calkyl or C-Chaloalkyl, wherein the C-Calkyl or C-Chaloalkyl is substituted by a 3- to 8-membered non-aromatic carbocyclic ...

Nrf2 REGULATORS

The present invention relates to aryl analogs, pharmaceutical compositions containing them and their use as NRF2 regulators. 2. The compound of claim 1 , wherein claim 1 ,{'sub': '1-3', 'B is benzotriazolyl which is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from —Calkyl and halo;'}{'sub': 2', '3, 'D is —C(O)OH, —C(O)NHSOCH, or tetrazolyl;'}{'sub': '1', 'Ris independently hydrogen or methyl or the two R, groups together with the carbon to which they are attached form a cyclopropyl group;'}{'sub': '2', 'Ris methyl or halo;'}{'sub': '2', 'Linker is —CH—;'}A is tetrahydrobenzoxazepinyl, tetrahydro-pyrido-oxazepinyl, piperidinyl, tetrahydrobenzazepinyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, or tetrahydrobenzodiazepinyl;{'sub': 1-3', '1-3, 'each of which is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from —Calkyl, halo, CN, and —OCalkyl;'}{'sub': 1-3', '2', '1-3', '3-7, 'and the piperidinyl is unsubstituted or additionally substituted by pyrazolyl or oxadiazolyl each of which is unsubstituted or further substituted by —Calkyl or, when A is piperidinyl, it is unsubstituted or substituted by —SOR, wherein R is —Calkyl, phenyl or Ccycloalkyl;'}{'sub': 2', '4-7', '2', '2', '5-7, 'and each of the imidazolyl, triazolyl, pyrazolyl, and tetrazolyl groups is independently unsubstituted or additionally substituted by one or two substituents independently selected from —CH—Ccycloalkyl, —CH-oxepane and —CH—C; and'}X is independently CH or N;or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein claim 1 ,{'sub': '1-3', 'B is benzotriazolyl which is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from —Calkyl and halo;'}D is —C(O)OH;{'sub': 1', '1, 'Ris independently hydrogen or methyl or the two Rgroups together with the carbon to which they are attached form a cyclopropyl group;'}{'sub': '2', 'Ris methyl or halo;'}{'sub': '2', 'Linker is —CH—;'}A ...

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O) 2 —, —C(═O)—, —O—, —C(R 6 )(R 7 )—, —N(R 5 )— or —C(═N(R 5 ))—; X is —O—, —N(R 5 )— or —C(R 6 )(R 7 )—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O) 2 —, —C(═O)— or —C(═NR 5 )—; U is a bond, —S(O)—, —S(O) 2 —, —C(O)—, —O—, —P(O)(OR 15 )—, —C(═NR 5 )—, —(C(R 6 )(R 7 )) b — or —N(R 5 )—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, U is not —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—; provided that when X is —N(R 5 )— and W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, then U is not a bond; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Cyclic Peptidomimetic Compounds as Immunomodulators

The present invention relates to cyclic peptidomimetic compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The invention also relates to derivatives of the therapeutic agents. The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them.

Macrocyclic Compounds And Metal Complexes For Bioimaging And Biomedical Applications

The present disclosure provides a novel class of macrocyclic compounds and their metal complexes formed with transition metal ion, lanthanide metal ions and other metal ions (e.g., Al, Ga, Y, In, Sn, Tl, Pb and Bi) and their applications in the fields of contrast agents, artificial nucleases, fluorescence probes, nuclear medicines and other biomedical applications in the therapeutics or diagnostics. 4. The compound of claim 1 , further comprising at least one group of formula (IV):{'br': None, 'sub': s', 't', 'p, '-W-(X—Y)—\u2003\u2003(IV)'}that bounds the compound of formula (I) to a biomolecule. [{'sub': 2', '2', '2', '2', '2', '2', '8', '2', '2', '8', '8', '8', '8', '8', '8', '8, 'W is —O—, —S—, —CH—, —SO—, SO—, —CO—, —NHNH—, —CONH—, —NHCO—, —NHCONH—, —CONHCO—, —NHCONHO—, —COO—, —COCH—, —CHCO—, —NHO—, —ONH—, —CH═CH—, —CHNH—, —NHCH—, —NH—, —NR, —NH(C═NH)NH—, —CH═N—, —CH═N—O—, —N═CH—, —SONH—, —NHSO—, —NH—CS—, —NHCSNH—, —NH(C═NH)NH—O—, —OCO—, —S—S—, —N═N—, alkynyl, methylene carbamate, methylene thiocarbamate, methylene isourea, methylene isothiourea, methylene guanidine, —C═C(R)—COOR, —C═C(R)—COR, —C═NH—, —C═NOH, —C═NR, —C═NOR, allyl-OCOR, allyl ester, phenylene, alkylene, ethynydiyl, ethylenediyl, a polymerizable group, a boron, a silicon, phosphorous, selenium, haloacetamido, isothiocyanate, maleimido, dichlorotriazinylamino, dichlorotriazinyl, thioester, pyridyldithio, aminooxy, amino, hydrazide, carboxylic acid, or acid halide;'}, {'sub': '8', 'Ris alkyl, cycloalkyl, or aryl;'}, 'X and Y are same or different and independently alkyl, cycloalkyl, aryl, or heterocylic, wherein any two carbon atoms are optionally interrupted with one or more N, O, S, Si, P, Se or B; and', 's, t, and p are an integer from 0 to 100., 'wherein5. The compound of claim 4 , wherein X and Y further comprises positively charged carboxylate or negatively charged ammonium moieties6. The compound of claim 4 , wherein the biomolecule is proteins claim 4 , protein-proteins claim 4 , ...

ELECTROLYTE-ADDITIVE FOR LITHIUM-ION BATTERY SYSTEMS

The invention relates to the use of compounds according to general formula (1), in particular 1,4,2-dioxoazol-5-on-derivatives, as additives in electrolytes for electrochemical energy sources such as lithium-ion-batteries, and compounds containing electrolytes according to general formula (1), in particular, 1,4,2-dioxoazol-5-on-derivatives. 2. The electrolyte as claimed in claim 1 , characterized in that Ris selected from the group consisting of CN C-C-alkyl claim 1 , C-C-phenyl and mixtures thereof claim 1 , wherein the C-C-alkyl and/or C-C-phenyl which are unsubstituted or monosubstituted or polysubstituted by fluorine.3. The electrolyte as claimed in claim 1 , characterized in that X is carbon and Ris selected from the group consisting of CH claim 1 , CF claim 1 , CN claim 1 , tert-butyl claim 1 , phenyl and mixtures thereof.4. The electrolyte as claimed in claim 1 , characterized in that the electrolyte contains the compound of the general formula (1) in an amount in the range from ≥0.1% by weight to ≤10% by weight claim 1 , preferably in the range from ≥0.5% by weight to ≤7% by weight claim 1 , more preferably in the range from ≥3% by weight to ≤5% by weight claim 1 , based on the total weight of the electrolyte.5. The electrolyte as claimed in claim 1 , characterized in that the solvent is selected from the group consisting of an unfluorinated organic solvent claim 1 , a partially fluorinated organic solvent claim 1 , an ionic liquid claim 1 , a polymer matrix and mixtures thereof.6. The electrolyte as claimed in claim 1 , characterized in that the solvent is an organic solvent selected from the group consisting of ethylene carbonate claim 1 , ethyl methyl carbonate claim 1 , propylene carbonate claim 1 , dimethyl carbonate claim 1 , diethyl carbonate claim 1 , acetonitrile claim 1 , propionitrile claim 1 , 3-methoxypropionitrile claim 1 , glutaronitrile claim 1 , adiponitrile claim 1 , pimelonitrile claim 1 , gamma-butyrolactone claim 1 , gamma-valerolactone ...

Macrocyclic urea and sulfamide derivatives as inhibitors of tafia

The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoaguability or fibrotic changes.

THERMAL PRE-IGNITION AGENT

The invention relates to a thermal pre-ignition agent which contains as components 20 to 50 wt. % of dinitrobenzofuroxane and 50 to 80 wt. % of an oxidizing agent and a nitrogen-containing compound. 1. A thermal pre-ignition agent , comprising 20 to 50 weight-% dinitrobenzofuroxane and 50 to 80% weight-% of an oxidizing agent and a compound comprising nitrogen.2. The thermal pre-ignition agent according to claim 1 , wherein it comprises 30 to 70 weight-% of an oxidizing agent selected from one or more of the list comprising nitrates of alkali metals and/or of alkaline earth metals and/or of ammonium claim 1 , perchlorates of alkali metals and/or of alkaline earth metals and/or of ammonium claim 1 , peroxides of alkali metals and/or of alkaline earth metals and/or of zinc.3. The thermal pre-ignition agent according to claim 1 , wherein it comprises 10 to 50 weight-% of a nitrogen-containing compound claim 1 , selected from one or more of the list comprising ammonium picrate claim 1 , aminoguanidinium picrate claim 1 , guanidinium picrate claim 1 , aminoguanidinium styphnate claim 1 , guanidinium styphnate claim 1 , nitroguanidine claim 1 , nitro amino guanidine claim 1 , nitrotriazolone claim 1 , derivates of tetrazol and/or the salts thereof claim 1 , nitraminotetrazole and/or the salts thereof claim 1 , aminoguanidine nitrate claim 1 , di-aminoguanidine nitrate claim 1 , tri-aminoguanidin nitrate claim 1 , guanidine nitrate claim 1 , dy-cyanidiamindine nitrate claim 1 , di-aminoguanidine-azotetrazolate.4. The thermal pre-ignition agent according to claim 1 , wherein it comprises 1 to 15 weight-% of a reducing agent selected from one or more of the list comprising aluminum claim 1 , titanium claim 1 , titanium hydride claim 1 , boron claim 1 , boron hydride claim 1 , zirconium claim 1 , zirconium hydride claim 1 , silicon claim 1 , graphite claim 1 , active carbon claim 1 , carbon black.5. The thermal pre-ignition agent according to claim 1 , wherein it comprises 1 ...

NEW MACROCYCLIC AMIDINOUREA DERIVATIVES, METHODS OF PREPARATION AND USES THEREOF AS CHITINASE INHIBITORS

The present invention relates to macrocyclic amidinourea derivatives of formula 8, methods of preparation and uses thereof, pharmaceutical compositions in particular to be used as chitinase inhibitors in the treatment of a fungal infection. 6. The compound according to wherein X is C(=0) and Y is CHor pharmaceutically acceptable salts thereof.8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13CandidaC. albicans, C. guilliermondii, C. krusei, C. parapsilosis, C. tropicalis, C. kefyrC. glabrata.. The method according to wherein the species is selected from the group consisting of: or14Candida. The method according to wherein the species is drug resistant.15Candida. The method according to wherein the species is resistant to fluconazole and/or voriconazole.16. (canceled)17. The method according to wherein the IL-13 and/or Th-2-mediated disease is a Th-2-mediated inflammation.18. The method according to wherein the IL-13 and/or Th-2-mediated disease is an allergic airway disease.19. A pharmaceutical composition comprising at least one compound according to and appropriate excipients or diluents.20. The pharmaceutical composition according to further comprising at least one therapeutic agent selected from the group consisting of: antifungal agent claim 19 , anti-inflammatory agent.21. The pharmaceutical composition according to wherein the further antifungal agent is selected from the group consisting of: azole family antifungal agent (fluconazole claim 20 , voriconazole) claim 20 , macrolides such as amphotericin claim 20 , polyene antifungals such as Amphotericin B claim 20 , Candicidin claim 20 , Filipin claim 20 , Hamycin claim 20 , Natamycin claim 20 , Nystatin claim 20 , Rimocidin claim 20 , Imidazole claim 20 , triazole claim 20 , and thiazole antifungals claim 20 , such as for imidazoles: Canesten (clotrimazole) claim 20 , Bifonazole claim 20 , Butoconazole claim 20 , Clotrimazole claim 20 , Econazole claim 20 , Fenticonazole claim 20 , ...

Macrocyclic Urea Derivatives as Inhibitors of TAFIa, Their Preparation and Their Use as Pharmaceuticals

The present invention relates to macrocydic urea derivatives of the formula I (I) in which R1, R2, R3, V and Y are as defined below. The compounds of the formula I are inhibitors of the enzyme TAFIa (activated thrombin-activatable fibrinolysis inhibitor). The invention further relates to the process for the preparation of the compounds of formula I and to the use thereof as medicaments. 2. The compound of claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , whereinV is —(CH2)4-; 'wherein phenyl is unsubstituted or substituted by one, two or three R15 groups;', 'Y is a covalent bond or phenyl,'}R1 is isopropyl;R2 is methyl; wherein Het is selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, furanyl and thiophenyl, bonded via a ring carbon atom to the methylene group to which R3 is attached, and', 'wherein Het and —(C4-C8)-cycloalkyl are unsubstituted or substituted by one two or three R15 groups; and, 'R3 is Het substituted by —NH2, or —(C4-C8)-cycloalkyl substituted by —NH2,'}each R15 group is independently hydrogen, —(C1-C4)-alkyl, —O—CF3, —NH2, —OH, —CF3 or halogen.3. The compound of claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , whereinV is —(CH2)4-;Y is a covalent bond or phenyl;R1 is isopropyl;R2 is methyl; andR3 is pyridinyl substituted by —NH2, cyclobutyl substituted by —NH2, or cyclopentyl substituted by —NH2.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein the compound is:(S)-3-(6-Amino-pyridin-3-yl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-aza-bicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)-ureido]-2-methyl-propionic acid;(S)-3-(3-Amino-cyclobutyl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10- ...

Extreme Ultraviolet Photoresist With High-Efficiency Electron Transfer

A method includes forming a photoresist layer over a substrate, wherein the photoresist layer includes a polymer, a sensitizer, and a photo-acid generator (PAG), wherein the sensitizer includes a resonance ring that includes nitrogen and at least one double bond. The method further includes performing an exposing process to the photoresist layer. The method further includes developing the photoresist layer, thereby forming a patterned photoresist layer. 1. A method comprising:forming a photoresist layer over a substrate, wherein the photoresist layer includes a polymer, a sensitizer, and a photo-acid generator (PAG), wherein the sensitizer includes a resonance ring that includes nitrogen and at least one double bond;performing an exposing process to the photoresist layer;performing a thermal treatment to the photoresist layer; anddeveloping the photoresist layer, thereby forming a patterned photoresist layer.2. The method of claim 1 , wherein the sensitizer is chemically bonded to the PAG.3. The method of claim 1 , wherein the resonance ring includes at least two nitrogen atoms.4. The method of claim 1 , wherein the sensitizer includes a second resonance ring containing nitrogen and at least one double bond.5. The method of claim 1 , wherein the sensitizer has an electron recombination energy within a range of about 165-170 kilocalories/mol.6. The method of claim 1 , wherein the sensitizer is an aromatic structure.7. The method of claim 1 , wherein the sensitizer includes a heterocyclic structure.8. The method of claim 1 , wherein the sensitizer includes a polar group of at least one of —OH claim 1 , —NH2 claim 1 , COOH claim 1 , and CONH2.9. The method of claim 1 , wherein the PAG comprises an absorb group that includes a structure with a plurality of rings claim 1 , wherein at least one of the rings is heterocyclic and includes at least one double bond.10. The method of claim 9 , wherein the structure includes one of: sulfur claim 9 , iodine claim 9 , or carbon.11 ...

METHOD FOR PRODUCING POLYISOCYANATES COMPRISING IMINOOXADIAZINEDIONE GROUPS AND USE OF THESE

The present invention relates to a method for producing polyisocyanates comprising iminooxadiazinedione groups, wherein at least one monomeric di- and/or tri-isocyanate is oligomerised in the presence of a) at least one catalyst, b) at least one additive (A) having a relative permittivity at 18° C. to 30° C. of less than 4.0, c) optionally further additives other than A. The invention relates further to a reaction system for producing polyisocyanates comprising iminooxadiazinedione groups, and to the use of an additive (A) having a relative permittivity at 18° C. to 30° C. of less than 4.0 for producing polyisocyanates comprising iminooxadiazinedione groups by catalysed modification of monomeric di- and/or tri-isocyanates. 1. A method for producing polyisocyanates containing iminooxadiazinedione groups , comprising oligomerizing at least one monomeric di- and/or tri-isocyanate in the presence ofa) at least one catalyst,b) at least one additive (A) having a relative permittivity at 18° C. to 30° C. of less than 4.0,c) optionally further additives other than A.2. A method according to claim 1 , wherein additive (A) is added to the monomeric di- and/or tri-isocyanate before it is brought into contact with the catalyst.3. The method according to claim 1 ,{'sub': 4', '30, 'wherein additive (A) is selected from the group consisting of a linear or branched, aliphatic, cycloaliphatic and/or araliphatic C-C-alkane.'}4. The method according claim 1 , wherein from 1 to 50 wt. % claim 1 , of additive (A) is included claim 1 , based on the mass of the monomeric di- and/or tri-isocyanate.5. The method according to claim 1 , wherein additive (A) has a relative permittivity at 18° C. to 30° C. of not more than 3.5 claim 1 , preferably of not more than 3.0 claim 1 , particularly preferably of not more than 2.8 or even not more than 2.5.6. The method according to claim 1 , wherein the monomeric di- and/or tri-isocyanate comprises an aliphatic diisocyanate.7. The method according to ...

PREPARATION METHOD FOR S-INDOXACARB

A catalyst and a method for preparing S-indoxacarb using the catalyst. The catalyst is prepared using 3-tert-butyl-5-(chloromethyl)salicylaldehyde and cyclohexanediamine as raw materials, where an original quinine catalyst such as cinchonine is replaced with the catalyst for application in the asymmetric synthesis of tert-butyl hydroperoxide and 5-chloro-2-methoxycarbonyl-1-indanone ester, greatly improving selection in the asymmetric synthesis process, with the S-enantiomer content increasing from 75% to over 98%, achieving the recycling of a high-efficiency chiral catalyst, and greatly reducing production costs. The synthesis process of the catalyst is simple and is favorable for industrialization, and lays good foundations for the production of high-quality indoxacarb. 2. The preparation method for S-indoxacarb according to claim 1 , comprising the steps of:adding tert-butyl hydroperoxide and 5-chloro-2-methoxycarbonyl-1-indanone ester to the polymerization catalyst solution obtained by the above method to carry out asymmetric synthesis, wherein a mole ratio of 5-chloro-2-methoxycarbonyl-1-indanone ester: 1 tert-butyl hydroperoxide:catalyst is 1:1.2-1.5:0.05-0.1; raising the temperature to 60-120° C. for reflux reaction for 4 hours, filtering the obtained mixture to recover polymer catalyst, the key intermediate 5-chloro-2-methoxycarbonyl-2-hydroxy-1-indanone is obtained by vacuum distillation of the filtrate, meanwhile, putting the recovered catalyst into toluene solvent to form suspension to continue to participate in the asymmetric synthesis reaction;after obtaining the above-mentioned 5-chloro-2-methoxycarbonyl-2-hydroxy-1-indanone, making it react with carbobenzoxyhydrazide and diethoxymethane according to the above-mentioned conventional synthesis route, and finally, with hydrogenating deprotection, synthesizing S-indoxacarb with 4-trifluoromethoxy phenyl carbamate.3. The preparation method for S-indoxacarb according to claim 1 , wherein the ...

1,2,4-Oxadiazole Derivatives as Immunomodulators

The present invention relates to methods of modulating an immune response mediated by a PD-1 signaling pathway and of treating a cancer or an infectious disease. A subject is administered a compound(s) or a pharmaceutically acceptable salt or pharmaceutically acceptable composition thereof of formula (I) 2. The method of claim 1 , wherein Q is O.3. The method of claim 1 , wherein Ris H.4. The method of claim 1 , wherein Ris —C(O)CH claim 1 , —C(O)CHCH claim 1 , —C(O)(CH)CH claim 1 , —C(O)(CH)CH claim 1 , —C(O)(CH)CHor —C(O)(CH)CH.5. The method of claim 1 , wherein Ris —CO-Aaa.7. The method according to claim 1 , wherein Aaa is an amino acid residue selected from Thr and Ser; wherein the C-terminus is a free terminus.9. The method according to claim 1 , wherein Rrepresents a side chain of an amino acid residue Ser or Thr.10. The method according to claim 1 , wherein Ris substituted with Calkyl.11. The method according to claim 1 , wherein Rrepresents a side chain of an amino acid residue Asn or Glu.12. The method according to claim 1 , wherein:{'sub': '1', 'Rrepresents a side chain of an amino acid residue Ser or Thr;'}{'sub': '2', 'Ris —CO-Aaa;'}Aaa is an amino acid residue selected from Thr and Ser; wherein the C-terminus is a free terminus; and{'sub': '3', 'Rrepresents a side chain of an amino acid residue Asn or Glu.'}13. The method according to claim 1 , wherein Rrepresents a side chain of an amino acid residue Ser.14. The method according to claim 1 , wherein Rrepresents a side chain of an amino acid residue Thr.15. The method according to claim 1 , wherein Aaa is Ser.16. The method according to claim 1 , wherein Aaa is Thr.17. The method according to claim 1 , wherein Rrepresents a side chain of an amino acid residue Asn.18. The method according to claim 1 , wherein Rrepresents a side chain of an amino acid residue Asp.19. The method according to claim 1 , wherein Rrepresents a side chain of an amino acid residue Gin.20. The method according to claim 1 , ...

Process for Preparing (E)-(5,6-Dihydro-1,4,2-Dioxazine-3-YL) (2-Hydroxyphenyl) Methanone O-Methyl Oxime

A process for preparing (E)-(5,6-dihydro-1,4,2-dioxazin-3-yl)(2-hydroxyphenyl)methanone O-methyl oxime is described which includes: (i) reacting benzofuran-3(2H)-one O-methyl oxime (1) with at least one nitrite selected from n-butyl nitrite and tert-butyl nitrite, in the presence of a metal alkoxide to form (2Z,32)-2,3-benzofuran-dione O3-methyl dioxime (2) as the predominant isomer; (ii) reacting the (2Z,3Z)-2,3-benzofuran-dione O-methyl dioxime (2) with 2-haloethanol to form (2Z,3Z)-benzofuran-2,3-dione 02-(2-hydroxyethyl) O3-methyl dioxime (3); and (iii) reacting the (2Z,3Z)-benzofuran-2,3-dione 02-(2-hydroxyethyl) & -methyl dioxime (3) with an acid to form (E)-(5,6-dihydro-1,4,2-dioxazin-3-yl)(2-hydroxyphenyl)methanone (9-methyl oxime (4);

Compositions comprising macrocycle derivatives incorporating bridged macrocycles and methods of producing and using same

Compositions are disclosed herein that include macrocycle derivatives incorporating bridged macrocycles. Also disclosed are methods of producing and using the compositions.

CYCLIC CARBONATE MONOMERS AND RING OPENED POLYCARBONATES THEREFROM

Eight-membered ring cyclic carbonates having an oxygen or an acylated nitrogen at position 6 were prepared by reaction of precursor diols with ethyl chloroformate. The cyclic carbonates undergo organocatalyzed ring opening polymerization. In one instance, the initial polymer formed comprises a carbonate repeat unit having a Boc-protected nitrogen in the polymer backbone. Deprotecting the nitrogen with acid forms a cationic carbonate repeat unit having a positive charged secondary ammonium nitrogen in the polymer backbone. 2. The compound of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , iso-propyl claim 1 , n-butyl claim 1 , sec-butyl claim 1 , t-butyl claim 1 , phenyl claim 1 , benzyl claim 1 , and allyl.5. The compound of claim 1 , wherein Ris ethyl.6. The compound of claim 1 , wherein Ris n-propyl.7. The compound of claim 1 , wherein Ris iso-propyl.8. The compound of claim 1 , wherein Ris n-butyl.9. The compound of claim 1 , wherein Ris sec-butyl.10. The compound of claim 1 , wherein Ris phenyl.11. The compound of claim 1 , wherein Ris benzyl.12. The compound of claim 1 , wherein Ris allyl.14. The polymer of claim 13 , wherein Ris selected from the group consisting of methyl claim 13 , ethyl claim 13 , n-propyl claim 13 , iso-propyl claim 13 , n-butyl claim 13 , sec-butyl claim 13 , t-butyl claim 13 , phenyl claim 13 , benzyl claim 13 , and allyl.15. The compound of claim 13 , wherein Ris methyl.16. The compound of claim 13 , wherein Ris t-butyl.17. The compound of claim 13 , wherein Ris ethyl.18. The compound of claim 13 , wherein Ris n-propyl.19. The compound of claim 13 , wherein Ris iso-propyl.20. The compound of claim 13 , wherein Ris n-butyl.21. The compound of claim 13 , wherein Ris sec-butyl.22. The compound of claim 13 , wherein Ris phenyl.23. The compound of claim 13 , wherein Ris benzyl.24. The compound of claim 13 , wherein Ris allyl. This invention was made under a joint research ...

Asparagine Endopeptidase (AEP) Inhibitors for Managing Cancer and Compositions Related Thereto

This disclosure relates to asparagine endopeptidase inhibitors for managing cancer and compositions related thereto. In certain embodiments, the asparagine endopeptidase inhibitors are substituted 3,7-dihydropurine-2,6-dione derivatives useful for treating or preventing metastasis, tumor growth, and/or cancer. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising an asparagine endopeptidase inhibitor and a pharmaceutically acceptable excipient. In certain embodiments, the disclosure relates to methods of treating a cancer comprising administering an effective amount of pharmaceutical composition a asparagine endopeptidase inhibitor disclosed herein to a subject in need thereof. 2. The compound of claim 1 , wherein R1 is alkyl.3. The compound of claim 1 , wherein R2 is alkyl.4. The compound of claim 1 , wherein R6 is mercapto.5. The compound of claim 1 , wherein R7 is alkyl.6. The compound of selected from1-ethyl-8-mercapto-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione;8-mercapto-1,3,7-trimethyl-3,7-dihydro-1H-purine-2, 6-dione; and1-benzyl-8-mercapto-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione.7. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.8. The pharmaceutical composition of in the form of a pill claim 7 , capsule claim 7 , tablet claim 7 , or saline aqueous buffer.9. The pharmaceutical composition of claim 7 , wherein the pharmaceutically acceptable excipient is selected from a saccharide claim 7 , disaccharide claim 7 , sucrose claim 7 , lactose claim 7 , glucose claim 7 , mannitol claim 7 , sorbitol claim 7 , polysaccharides claim 7 , starch claim 7 , cellulose claim 7 , microcrystalline cellulose claim 7 , cellulose ether claim 7 , hydroxypropyl cellulose (HPC) claim 7 , xylitol claim 7 , sorbitol claim 7 , maltito claim 7 , gelatin claim 7 , polyvinylpyrrolidone (PVP) claim 7 , polyethylene glycol (PEG) claim 7 , hydroxypropyl methylcellulose (HPMC) claim 7 , crosslinked ...

1,2,4-Oxadiazole Derivatives as Immunomodulators

The present invention relates to pharmaceutical compositions of 1,2,4-oxadiazole compounds or a pharmaceutically acceptable salt thereof of formula (I) This application is a continuation under 35 U.S.C. § 120 of pending application U.S. Ser. No. 16/806,872, filed Mar. 2, 2020, which is a continuation under 35 U.S.C. § 120 of U.S. Ser. No. 16/192,030, filed Nov. 15, 2018, now U.S. Pat. No. 10,590,093, which is a continuation under 35 U.S.C. § 120 of application U.S. Ser. No. 15/713,671, filed Sep. 24, 2017, now U.S. Pat. No. 10,173,989, which is a continuation under 35 U.S.C. § 120 of U.S. Ser. No. 15/298,539, filed Oct. 20, 2016, now U.S. Pat. No. 9,771,338, which is a continuation under 35 U.S.C. § 120 of application U.S. Ser. No. 14/478,759, filed Sep. 5, 2014, now abandoned, which claims benefit of priority of Indian provisional application number 4011/CHE/2013, filed on Sep. 6, 2013, now abandoned, and for which a certified copy thereof is found in the file wrapper of U.S. Ser. No. 15/298,539, the entirety of all of which are hereby incorporated by reference.The present invention relates to 1,2,4-oxadiazole and 1,2,4-thiadiazole compounds and their derivatives therapeutically useful as immune modulators. The invention also relates to pharmaceutical compositions comprising the said 1,2,4-oxadiazole and 1,2,4-thiadiazole compounds and their derivatives as therapeutic agents.Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. PD-1 and its ligands are broadly expressed and exert a wider range of immunoregulatory roles in T cells activation and tolerance compared with other CD28 members. PD-1 and its ligands are involved in attenuating infectious immunity and tumor immunity, and facilitating chronic infection and tumor progression. The biological significance of PD-1 and its ligand suggests the therapeutic potential of manipulation of PD-1 pathway against various ...

CREATINE PRODRUGS, COMPOSITIONS AND METHODS OF USE THEREOF

The invention describes membrane permeable creatine prodrugs, pharmaceutical compositions comprising membrane permeable creatine prodrugs, and methods of treating diseases such as ischemia, heart failure, neurodegenerative disorders and genetic disorders affecting the creatine kinase system comprising administering creatine prodrugs or pharmaceutical compositions thereof. The invention also describes treating a genetic disease affecting the creatine kinase system, such as, for example, a creatine transporter disorder or a creatine synthesis disorder comprising administering creatine prodrugs or pharmaceutical compositions thereof. 2. The compound of claim 1 , wherein each n is independently the integer 1.3. The compound of claim 1 , wherein each n is independently the integer 2.4. The compound of claim 1 , wherein each R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Ris independently Calkyl claim 1 , substituted Calkyl claim 1 , Ccycloalkyl claim 1 , substituted Ccycloalkyl claim 1 , Caryl or substituted Caryl.5. The compound of claim 1 , wherein each R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Ris independently hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , sec-butyl claim 1 , tert-butyl claim 1 , n-pentyl claim 1 , isopentyl claim 1 , sec-pentyl claim 1 , neopentyl claim 1 , dodecyl claim 1 , 1 claim 1 ,1-dimethoxyethyl claim 1 , 1 claim 1 ,1-diethoxyethyl claim 1 , phenyl claim 1 , 4-methoxyphenyl claim 1 , benzyl claim 1 , phenethyl claim 1 , styryl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , 2-pyridyl claim 1 , 3-pyridyl or 4-pyridyl.6. The compound of claim 1 , wherein each R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Ris independently hydrogen claim 1 , methyl claim 1 ...

Simplified Structural Mimetics of AIPS as Quorum Sensing Inhibitors

Compounds that regulate quorum sensing in bacteria and in particular in are provided. Compounds are described in formulas I, II, III, IV, V and VI herein. One or more compounds herein can be employed to inhibit QS and to thus inhibit virulence in bacteria and in particular in Compounds herein and pharmaceutical compositions containing one or more of these compounds are useful, for example, in treating infections of bacteria and in particular of Methods for treating such bacterial infections are provided. 3. The compound of claim 2 , wherein:{'sub': 1', '2', 'n, 'Lis —(CH)—, where n is 2-9 or 3-8, and all R are H;'}{'sub': 1', '2', 'n', '3, "Lis —(CH)—, where n is 2-9 or 3-8, and at least one of the R's are CH;"}{'sub': 1', '2', 'n', '3', '1', '2, "Lis —(CH)—, where n is 2-9 or 3-8, at least one of the R's are CHand Xand Xare selected from sec-butyl, isobutyl, benzyl, p-OH-benzyl or 3-indolylmethyl;"}{'sub': '1', 'Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and all R are H;'}{'sub': 1', '3, "Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and at least one of the R's are CH; or"}{'sub': 1', '3', '1', '2, "Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and at least one of the R's are CHand Xand Xare selected from sec-butyl, isobutyl, optionally-substituted benzyl, cycloalkylalkyl or 3-indolylmethyl."}4. The compound of claim 1 , wherein W is S.5. The compound of claim 1 , wherein W is NH.6. The compound of claim 1 , wherein W is NCH.7. The compound of claim 1 , where —W—CO— is a double bond.8. The compound of claim 1 , wherein Xand Xare selected from sec-butyl claim 1 , isobutyl claim 1 , benzyl claim 1 , p-OH-benzyl claim 1 , p-F-benzyl claim 1 , p-Cl-benzyl claim 1 , m-F-benzyl claim 1 , m-Cl-benzyl claim 1 , cyclohexyl claim 1 , cyclopentyl claim 1 , or 3-indolylmethyl.9. The compound of claim 1 , wherein Xis selected from optionally-substituted benzyl and Xis selected from cyclohexylmethyl or cyclopentylmethyl.10. The compound of ...

CONJUGATED LIPOMERS AND USES THEREOF

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): 121-. (canceled)23. The conjugated lipomer of claim 22 , wherein each instance of Ris independently hydrogen or a group of the formula (iii′).24. The conjugated lipomer of claim 22 , wherein each instance of Ris independently substituted or unsubstituted alkyl; substituted or unsubstituted heteroalkyl; or a hydrophilic polymer.2528-. (canceled)29. The conjugated lipomer of claim 22 , wherein the dashed curved line claim 22 , together with G and Y claim 22 , is a covalent bond.32. The conjugated lipomer of claim 22 , wherein the lipomer comprises at least one instance of the group of the formula (vi).34. The conjugated lipomer of claim 22 , wherein the lipomer comprises at least one instance of the group of the formula (vii) claim 22 , (viii) claim 22 , or (ix).38. A composition comprising one or more conjugated lipomers of claim 22 , and claim 22 , optionally claim 22 , an excipient.39. The composition of claim 38 , wherein the composition is a pharmaceutical composition or a cosmetic composition.40. The composition of claim 38 , wherein the composition further comprises an agent.41. The composition of claim 40 , wherein the agent is an organic molecule claim 40 , inorganic molecule claim 40 , nucleic acid claim 40 , protein claim 40 , peptide claim 40 , polynucleotide claim 40 , targeting agent claim 40 , an isotopically labeled chemical compound claim 40 , vaccine claim 40 , or an immunological agent.42. The composition of claim 41 , wherein the agent is a polynucleotide claim 41 , and the polynucleotide is DNA or RNA.43. The composition of claim 42 , wherein the RNA is RNAi claim 42 , dsRNA claim 42 , siRNA claim 42 , shRNA claim 42 , miRNA claim 42 , or antisense RNA.4449-. (canceled)5153-. (canceled)54. A method of treating ...

Extreme Ultraviolet Photoresist With High-Efficiency Electron Transfer

A method includes forming a photoresist layer over a substrate, wherein the photoresist layer includes a polymer, a sensitizer, and a photo-acid generator (PAG), wherein the sensitizer includes a resonance ring that includes nitrogen and at least one double bond. The method further includes performing an exposing process to the photoresist layer. The method further includes developing the photoresist layer, thereby forming a patterned photoresist layer.

Nrf2 REGULATORS

Provided are aryl analogs, pharmaceutical compositions containing them and their use as NRF2 regulators. 2. The compound of claim 1 , wherein claim 1 ,{'sub': 2', '2', '1-3, 'B is benzotriazolyl or —(CH)triazolyl each of which may be unsubstituted or substituted by 1, 2, or 3 substituents independently chosen from: —Calkyl and halo;'}{'sub': 2', '3, 'D is —C(O)OH, —C(O)NHSOCH, or tetrazolyl;'}{'sub': 1', '1, 'Ris independently hydrogen or methyl or the two Rgroups together with the carbon to which they are attached form a cyclopropyl group;'}{'sub': '2', 'Ris methyl or halo;'}{'sub': '2', 'Linker is —CH—;'}A is tetrahydrobenzoxazepinyl, tetrahydro-pyrido-oxazepinyl, piperidinyl, tetrahydrobenzazepinyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, or tetrahydrobenzodiazepinyl;{'sub': 1-3', '1-3, 'All of which may be unsubstituted or substituted by 1, 2, or 3 substituents independently chosen from —Calkyl, halo, CN, or —OCalkyl;'}{'sub': 1-3', '2', '1-3', '3-7, 'And the piperidinyl may additionally be substituted by pyrazolyl or oxadiazolyl each of which may be further substituted by —Calkyl or, when A is piperidinyl, it may be substituted by —SOR, wherein R is —Calkyl, phenyl or Ccycloalkyl;'}{'sub': 2', '4-7', '2', '2', '5-7, 'And the imidazolyl, triazolyl, pyrazolyl, and tetrazolyl groups may be additionally independently substituted by —CH—Ccycloalkyl, —CH-oxepane or a —CH—C; and'}X is independently CH or N;or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein claim 1 ,{'sub': 2', '2', '1-3, 'B is benzotriazolyl, or —(CH)triazolyl each of which may be unsubstituted or substituted by 1, 2, or 3 substituents independently chosen from—Calkyl and halo;'}D is —C(O)OH;{'sub': 1', '1, 'Ris independently hydrogen or methyl or the two Rgroups together with the carbon to which they are attached form a cyclopropyl group;'}{'sub': '2', 'Ris methyl or halo;'}{'sub': '2', 'Linker is —CH—;'}A is tetrahydrobenzoxazepinyl, tetrahydro-pyrido-oxazepinyl ...

Method for producing polyisocyanates and use thereof

The invention relates to a method for modifying isocyanates using catalysts having a water content not exceeding 1,000 ppm.

Radiofluorinated carboximidamides as ido targeting pet tracer for cancer imaging

Radiofluorinated carboximidamides are disclosed as selective IDO enzyme radioligands and generate specific binding in accordance with IDO expression in vitro. MicroPET experiments indicate [18F]IDO49 specifically accumulate in IDO-expressing tumors which confirmed by Western blot and IHC analysis supported. Using Hela tumor bearing models with IFN-γ treatment confirmed that [18F]IDO49 accumulation in the IFN-γ treatment tumor mouse. These results can have implications that [18F]IDO49 has substantial potential as an imaging agent that targets IDO in tumors.

Guanine-rich oligonucleotides

This invention relates to methods for oligonucleotide synthesis, specifically the synthesis of oligonucleotides that contain a high content of guanine monomers. In more detail, the invention relates to a method for coupling a nucleoside phosphoramidite during the synthesis of an oligonucleotide to a universal support, to a first nucleoside, or to an extending oligonucleotide.

CONJUGATED LIPOMERS AND USES THEREOF

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): 2. The conjugated lipomer of claim 1 , wherein each instance of Ris independently hydrogen or a group of Formula (iii′).3. The conjugated lipomer of claim 1 , wherein each instance of Ris independently substituted or unsubstituted alkyl; substituted or unsubstituted heteroalkyl; or a hydrophilic polymer.4. The conjugated lipomer of claim 1 , wherein at least one instance of Ris substituted or unsubstituted alkyl.5. The conjugated lipomer of claim 1 , wherein the dashed curved line claim 1 , together with G and Y claim 1 , is a covalent bond.12. A composition comprising one or more conjugated lipomers of claim 1 , and claim 1 , optionally claim 1 , an excipient.13. The composition of claim 12 , wherein the composition is a pharmaceutical composition or a cosmetic composition.14. The composition of claim 12 , wherein the composition further comprises an agent.15. The composition of claim 14 , wherein the agent is an organic molecule claim 14 , inorganic molecule claim 14 , protein claim 14 , peptide claim 14 , polynucleotide claim 14 , targeting agent claim 14 , isotopically labeled chemical compound claim 14 , vaccine claim 14 , or immunological agent.16. The composition of claim 15 , wherein the agent is a polynucleotide claim 15 , and the polynucleotide is DNA or RNA.17. The composition of claim 16 , wherein the RNA is RNAi claim 16 , dsRNA claim 16 , siRNA claim 16 , shRNA claim 16 , miRNA claim 16 , or antisense RNA.18. The composition of claim 12 , wherein the one or more conjugated lipomers are in the form of a particle.19. The composition of claim 14 , wherein the agent is a polynucleotide that encodes a protein or peptide. The present application is a continuation of and claims priority under 35 U.S.C. §120 to U.S. ...

COMPOUNDS HAVING ANTIINFECTIVE, ANTITUMORAL AND ANTIFUNGAL ACTIVITY

The invention relates to novel compounds and their use in medicine, particularly in treating and/or preventing infections caused by a bacterium, fungus or virus or in treating and/or preventing cancer. Additionally, the invention relates to a process for obtaining the compounds of the invention. 3. The compound according to wherein Rand Rare the same group claim 1 , or a pharmaceutically acceptable salt claim 1 , stereoisomer or solvate thereof.4. The compound according to claim 1 , wherein Rand Rare —(CH)—CH claim 1 , or a pharmaceutically acceptable salt claim 1 , stereoisomer or solvate thereof.6. The compound according to claim 1 , wherein R is a methyl group or —(CH)—COOH claim 1 , or a pharmaceutically acceptable salt claim 1 , stereoisomer or solvate thereof.8. (canceled)9. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable excipient.1024-. (canceled)25. A method for the prevention and/or the treatment of an infection caused by a bacterium claim 1 , fungus or virus in a subject in need thereof for the prevention and/or the treatment of cancer in a subject in need thereof comprising the administration of a compound as defined in .26. The method according to wherein the bacterium is a Gram positive bacterium or a Gram-negative bacterium.27. The method according to claim 26 , wherein the Gram positive bacterium is from phylum Actinobacteria or from phylum Firmicutes or wherein the Gram negative bacterium is from phylum proteobacteria.28Nocardia, TsukamurellaMycobacteriumStaphylococcus, BacillusEnterococcus.. The method according to wherein the bacterium from phylum Actinobacteria is a bacterium from genus or and/or the bacterium from phylum Firmicutes is a bacterium from genus or29Acinetobacter, PseudomonasEscherichia.. The method according to wherein the bacterium from phylum proteobacteria is from genus or30NocardiaN. carneaN. cyriacigeorgicaTsukamurellaT. pulmonisMycobacteriumM. chelonae, M. abscessusM. ...

Urea derivative or pharmacologically acceptable salt thereof

The present invention provides a urea compound or a pharmacologically acceptable salt thereof that has a formyl peptide receptor like 1 (hereinafter may be abbreviated as FPRL1) agonist effect, a pharmaceutical composition containing the urea compound or the pharmacologically acceptable salt thereof, and a pharmaceutical use thereof. It has been found that a urea derivative represented by the general formula (I) below or a pharmacologically acceptable salt thereof has a superior FPRL1 agonist effect. Compound (I) or a pharmacologically acceptable salt thereof is highly useful for treatment, prevention, or suppression of inflammatory diseases, chronic airway diseases, cancers, septicemia, allergic symptoms, HIV retrovirus infection, circulatory disorders, neuroinflammation, nervous disorders, pains, prion diseases, amyloidosis, immune disorders and the like.

1,2,4-Oxadiazole Derivatives as Immunomodulators

The present invention relates to methods of modulating an immune response mediated by a PD-1 signaling pathway and of treating a cancer or an infectious disease. A subject is administered a compound(s) or a pharmaceutically acceptable salt or pharmaceutically acceptable composition thereof of formula (I) 2. The method according to claim 1 , wherein Q is O.3. The method according to claim 1 , wherein Ris H.4. The method according to claim 1 , wherein Ris —C(O)CH claim 1 , —C(O)CHCH claim 1 , —C(O)(CH)CH claim 1 , —C(O)(CH)CH claim 1 , —C(O)(CH)CH claim 1 , or —C(O)(CH)CH.5. The method according to claim 1 , wherein Ris —CO-Aaa.7. The method according to claim 1 , wherein Aaa is the amino acid residue Thr or Ser; wherein the C-terminus is the free terminus.9. The method according to claim 1 , wherein Rrepresents the side chain of an amino acid residue Ser or Thr.10. The method according to claim 1 , wherein Ris substituted with Calkyl.11. The method according to claim 1 , wherein Rrepresents the side chain of the amino acid residue Asn or Glu.12. The method according to claim 1 , wherein:{'sub': '1', 'Rrepresents the side chain of an amino acid residue Ser or Thr;'}{'sub': '2', 'Ris —CO-Aaa;'}Aaa is the amino acid residue Thr or Ser; wherein the C-terminus is a free terminus; and{'sub': '3', 'Rrepresents the side chain of the amino acid residue Asn or Glu.'}13. The method according to claim 1 , wherein Rrepresents the side chain of the amino acid residue Ser.14. The method according to claim 1 , wherein Rrepresents the side chain of the amino acid residue Thr.15. The method according to claim 1 , wherein Aaa is Ser.16. The method according to claim 1 , wherein Aaa is Thr.17. The method according to claim 1 , wherein Rrepresents the side chain of the amino acid residue Asn.18. The method according to claim 1 , wherein Rrepresents the side chain of the amino acid residue Asp.19. The method according to claim 1 , wherein Rrepresents the side chain of the amino acid ...

Novel cyclic depsipeptide derivatives and harmful organism control agents comprising the same

An objective of the present invention is to provide novel cyclic depsipeptide derivatives and harmful organism control agents including the same as each other. Specifically, the present invention provides compounds represented by formula (1) or stereoisomers thereof, harmful organism control agents containing them, and a process for producing them.

Intermediates for macrocyclic compounds

The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n 1 , m, p Z 1 , Z 2 , and Z 3 are as described in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.

Lithium Air Secondary Battery

A lithium air secondary battery is allowed to operate as a high-capacity secondary battery, thereby implementing high output and a large discharge capacity. A lithium air secondary battery includes an air electrode using oxygen in the air as a positive electrode active material, a negative electrode using metallic lithium or a lithium-containing material as a negative electrode active material, and an organic electrolyte placed between the air electrode and the negative electrode and including a lithium salt. The organic electrolyte includes a crown ether compound having an azo group as an additive. 1. A lithium air secondary battery , comprising: a positive electrode using oxygen as a positive electrode active material; a negative electrode using metallic lithium or a lithium-containing material as a negative electrode active material; and an organic electrolyte placed between the positive electrode and the negative electrode , and including a lithium salt , wherein the organic electrolyte includes a crown ether compound having an azo group.2. The lithium air secondary battery according to claim 1 , wherein the crown ether compound is any of 1-aza-15-crown-5-ether claim 1 , 1-aza-18-crown-6-ether claim 1 , 4 claim 1 ,13-diaza-18-crown-6-ether claim 1 , N claim 1 ,N′-dibenzyl-4 claim 1 ,13-diaza-18-crown-6-ether claim 1 , and N-phenyl aza-15-crown-5-ether. The present invention relates to a technology of a lithium air secondary battery. More particularly, the present invention relates to a lithium air secondary battery which is smaller in size and more lightweight than conventional secondary batteries such as a lead storage battery and a lithium ion battery, and can implement far larger discharge capacity.Reportedly, a lithium air secondary battery using oxygen in the air as a positive electrode active material is constantly supplied with oxygen from the outside of the battery, and can be filled with a large amount of metallic lithium of a negative electrode active ...

Solid-Phase Supports and Uses Thereof

The present disclosure relates to solid-phase azide supports, methods for making solid-state azide supports, and methods for capturing alkynes using the same. The present disclosure also relates to kits for solid-phase azide supports

PROCESS FOR PREPARING FLUOXASTROBIN

The disclosure includes a process for preparing fluoxostrobin which includes: 115-. (canceled)18. The process of claim 16 , wherein the alkyl nitrite is n-butyl nitrite or t-butyl nitrite.19. The process of claim 16 , wherein the acid is hydrochloric acid claim 16 , sulfuric acid claim 16 , methanesulfonic acid claim 16 , or phosphoric acid claim 16 , or a combination thereof.20. The process of claim 16 , wherein a content of the (3E)-2 claim 16 ,3-benzofuran-dione O-methyl dioxime (11A) in a mixture of (3E)- and (3Z)-isomers is from 90% to 94%.21. The process of wherein the base reacted with (12A) is a metal hydroxide.22. The process of claim 18 , where the base is lithium hydroxide claim 18 , sodium hydroxide claim 18 , potassium hydroxide claim 18 , or a combination thereof.23. The process of claim 17 , wherein the base used to react the benzofuran-3(2H)-one O-methyl oxime (10) with an alkyl nitrite is a metal hydroxide claim 17 , a metal hydride claim 17 , a metal alkoxide claim 17 , or a combination of the foregoing.24. The process of claim 17 , wherein the alkyl nitrite is n-butyl nitrite or t-butyl nitrite.25. The process of claim 17 , wherein the base in the reacting benzofuran-3(2H)-one O-methyl oxime (10) with an alkyl nitrite comprises a metal hydroxide claim 17 , a metal hydride claim 17 , and a metal alkoxide.26. The process of claim 17 , wherein a content of the (3Z)-2 claim 17 ,3-benzofuran-dione O-methyl dioxime (11B) in a mixture of (3E)- and (3Z)-isomers is 94% to 98%.27. The process of claim 17 , wherein the reaction of (Z)-2 claim 17 ,3-benzofuran-dione O-methyl dioxime (11B) with 2-haloethanol to form (Z)-benzofuran-2 claim 17 ,3-dione O-(2-hydroxyethyl) O-methyl dioxime (12B) may be carried out at a temperature of about 20° C. to about 100° C.28. The process of claim 17 , wherein the base reacted with (Z)-benzofuran-2 claim 17 ,3-dione O-(2-hydroxyethyl) O-methyl dioxime (12B) to form (2)-(5 claim 17 ,6-dihydro-1 claim 17 ,4 claim 17 ,2- ...

Macrocyclic Ghrelin Receptor Modulators and Methods of Using the Same

The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders. 2. The method of claim 1 , wherein the gastroparesis is diabetic gastroparesis or postsurgical gastroparesis syndrome.3. The method of claim 1 , wherein the compound is administered orally.4. The method of claim 1 , wherein the compound is administered parenterally.5. The method of claim 1 , wherein the subject is a mammal.6. The method of claim 1 , wherein the subject is a human.7. The method of claim 1 , wherein the subject is a horse.8. The method of claim 1 , wherein the compound is co-administered with an additional agent useful for stimulating gastrointestinal motility.10. The method of claim 9 , wherein the gastroparesis is diabetic gastroparesis or postsurgical gastroparesis syndrome.11. The method of claim 9 , wherein the compound is administered orally.12. The method of claim 9 , wherein the compound is administered parenterally.13. The method of claim 9 , wherein the subject is a mammal.14. The method of claim 9 , wherein the subject is a human.15. The method of claim 9 , wherein the subject is a horse.16. The method of claim 9 , wherein the compound is co-administered with an additional agent useful for stimulating gastrointestinal motility. This application is a continuation of U.S. patent application Ser. No. 15/178, ...

CONJUGATED LIPOMERS AND USES THEREOF

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): 24-. (canceled)5. The conjugated lipomer of claim 1 , wherein the conjugated lipomer is prepared from a polyethyleneimine polymer having a number average molecule weight (Mn) of less than 800 g/mol.6. The conjugated lipomer of claim 1 , wherein each instance of Ris independently hydrogen or a group of the formula (iii′).7. The conjugated lipomer of claim 1 , wherein Z is hydrogen or a group of the formula (iii′).8. The conjugated lipomer of claim 1 , wherein n is an integer of 3 to 5 claim 1 , inclusive.9. The conjugated lipomer of claim 1 , wherein each instance of Ris independently hydrogen; a substituted or unsubstituted polyethyleneimine; or a group of the formula (iii′).10. The conjugated lipomer of claim 1 , wherein at least one Lgroup is of the formula (ii).1112-. (canceled)13. The conjugated lipomer of claim 1 , wherein each instance of Ris substituted or unsubstituted alkyl.1437-. (canceled)38. A composition comprising one or more conjugated lipomers of claim 1 , and claim 1 , optionally claim 1 , an excipient.39. The composition of claim 38 , wherein the composition is a pharmaceutical composition or a cosmetic composition.40. The composition of claim 38 , wherein the composition further comprises an agent.41. The composition of claim 40 , wherein the agent is an organic molecule claim 40 , inorganic molecule claim 40 , nucleic acid claim 40 , protein claim 40 , peptide claim 40 , polynucleotide claim 40 , targeting agent claim 40 , an isotopically labeled chemical compound claim 40 , vaccine claim 40 , or an immunological agent.42. The composition of claim 41 , wherein the agent is a polynucleotide claim 41 , and the polynucleotide is DNA or RNA.43. The composition of claim 42 , wherein the RNA is RNAi claim 42 , dsRNA ...

PYRIDOMYCIN BASED COMPOUNDS EXHIBITING AN ANTITUBERCULAR ACTIVITY

Formula (1), Xrepresents O or NR, Xrepresents O or NR, Xrepresents O or NR, Rrepresents H or Cto Calkyl, Rrepresents H, or linear or branched C-Calkyl optionally including one or more heteroatoms, cyclopropyl, cyclobutyl, cyclohexyl or oxetanyl or amino acid side chain or protected amino acid side chain, or Rand Rmay form together a saturated, partly saturated or unsaturated 5 or 6 membered ring system, optionally substituted, Rrepresents H, cyclopentyl, cyclohexyl, aryl or hydroxyaryl, aryl or hydroxyaryl being optionally substituted by fluorine, or linear or branched Cto Calkyl optionally including a hetero atom, Rrepresents phenyl or 5- or 6-membered heterocycles including one or more nitrogen or oxygen atoms optionally substituted with 1 to 4, respectively 5 fluorine atoms, and Rrepresents H, or linear or branched alkyl chain having 1 to 3 carbon atoms. 2. Compound according to claim 1 , wherein Rrepresents H claim 1 , or a linear or branched C-Calkyl optionally comprising one or more heteroatoms claim 1 , cyclopropyl claim 1 , cyclobutyl or oxetanyl or an amino acid side chain or a protected amino acid side chain claim 1 , or{'sub': 1', '2, 'Rand Rmay form together a 5 or 6 membered ring system which may be saturated, partly saturated or unsaturated, said ring system being optionally substituted.'}3. Compound according to claim 1 , wherein Xrepresents O.4. Compound according to claim 1 , wherein Xrepresents NRand Ris hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl or isopropyl.5. Compound according to claim 1 , wherein Ris the side chain of an amino acid selected from the group of alanine claim 1 , valine claim 1 , leucine claim 1 , isoleucine claim 1 , tryptophan claim 1 , phenylalanine claim 1 , methionine claim 1 , serine or a protected serine claim 1 , tyrosine or a protected tyrosine claim 1 , threonine or a protected threonine claim 1 , cysteine or a protected threonine claim 1 , asparagine claim 1 , glutamin claim 1 , aspartate claim 1 , ...

MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIA

The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes. 2. (canceled)3. A compound of the formula (I) as claimed in claim 1 , or a stereoisomer thereof or a physiologically tolerated salt of any of the foregoing compounds claim 1 , where{'sub': '2', 'X is —C(O)— or —SO—;'}U is oxygen atom, sulfur atom, or NH;{'sub': 0', '4, 'A is —(C-C)-alkylene-;'}{'sub': 2', '8, 'V is —(C-C)-alkylene,'}{'sub': 1', '2, 'D is —(C-C)-alkylene-;'}Y is{'sub': 3', '6, '1) —(C-C)-cycloalkyl, wherein said cycloalkyl is substituted independently of one another once, twice or three times by R15,'}{'sub': 6', '14, '2) —(C-C)-aryl, wherein said aryl is selected from the group of phenyl, naphthyl, anthryl or fluorenyl, and in which aryl is unsubstituted or substituted independently of one another once, twice or three times by R15, or'}3) Het, wherein Het is selected from the group consisting of acridinyl, azepinyl, azetidinyl, aziridinyl, benzimidazalinyl, benzimidazolyl, benzo[1,3]dioxolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, chromanyl, chromenyl, cinnolinyl, deca-hydroquinolinyl, dibenzofuranyl, dibenzothiophenyl, dihydrofuran[2,3-b]-tetrahydrofuranyl, dihydrofuranyl, dioxolyl, dioxanyl, 2H, 6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, ...

PYRIDINE DERIVATIVES AS SOFT ROCK INHIBITORS

The present invention relates to new kinase inhibitors, more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including Respiratory and Gastro-Intestinal diseases. 112.-. (canceled)14. The method of treatment according to claim 13 , wherein Cy is selected from aryl and heteroaryl claim 13 , wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halo claim 13 , hydroxyl claim 13 , oxo claim 13 , carbonyl claim 13 , amino claim 13 , amido claim 13 , cyano claim 13 , aryl claim 13 , heteroaryl claim 13 , Ccycloalykl claim 13 , Cheterocyclyl claim 13 , Calkylamino claim 13 , Calkyl claim 13 , di(Calkyl)amino claim 13 , Calkoxy claim 13 , halo-Calkoxy claim 13 , halo-Calkyl claim 13 , thiol claim 13 , Calkylthio claim 13 , carboxylic acid claim 13 , acylamino claim 13 , Calkyl ester claim 13 , carbamate claim 13 , thioamido claim 13 , urea claim 13 , and sulfonamide.15. The method of treatment according to claim 13 , wherein Cy is aryl claim 13 , wherein said aryl is optionally substituted with one or more substituents selected from the group consisting of halo claim 13 , hydroxyl claim 13 , oxo claim 13 , carbonyl claim 13 , amino claim 13 , amido claim 13 , cyano claim 13 , aryl claim 13 , heteroaryl claim 13 , Ccycloalkyl claim 13 , Cheterocyclyl claim 13 , Calkylamino claim 13 , Calkyl claim 13 , di(Calkyl)amino claim 13 , Calkoxy claim 13 , halo-Calkoxy claim 13 , halo-Calkyl ...

PROCESS FOR CONTINUOUS ISOCYANATE MODIFICATION

A process for continuous preparation of oligomeric or polymeric isocyanates by catalytic modification of monomeric di- and/or triisocyanates, characterized in that at least one isocyanate component A and at least one catalyst component B are combined continuously in a reaction apparatus and conducted through the reaction apparatus as a reaction mixture, the residence time distribution being characterized according to the dispersion model by Bo (Bodenstein number) above 40, preferably above 60 and most preferably above 80. 113.-. (canceled)14. A process for the continuous preparation of oligomeric or polymeric isocyanates by catalytic modification of monomeric diisocyanates and/or triisocyanates , comprising continuously combining at least one isocyanate component A and at least one catalyst component B in a reaction apparatus and conveying as reaction mixture through the reaction apparatus , where the residence time distribution according to the dispersion model is characterized by a Bo (Bodenstein number) above 40.15. The process as claimed in claim 14 , wherein the isocyanate component and the catalyst component are combined using an intensive mixer.16. The process as claimed in claim 14 , wherein not only the components A and B but also further compounds are present in the reaction mixture or these are introduced along the reaction section claim 14 , where these are claim 14 , in the first case claim 14 , bonding agents claim 14 , stabilizers or fluidizers and in the second case claim 14 , bonding agents claim 14 , stabilizers claim 14 , fluidizers claim 14 , diisocyanates or triisocyanates different from A claim 14 , catalysts different from B or catalyst-deactivating materials.17. The process as claimed in claim 14 , wherein intensive mixing of all components is effected by use of mixing elements along the residence section.18. The process as claimed in claim 14 , wherein it is carried out in the temperature range from 0° C. to +200° C. claim 14 , with a ...

COMPOSITIONS COMPRISING MACROCYCLE DERIVATIVES INCORPORATING BRIDGED MACROCYCLES AND METHODS OF PRODUCING AND USING SAME

Compositions are disclosed herein that include macrocycle derivatives incorporating bridged macrocycles. Also disclosed are methods of producing and using the compositions. 2. The composition of claim 1 , further comprising a metal with which the compound is complexed claim 1 , wherein the metal is selected from the group consisting of a transition metal claim 1 , a main group metal claim 1 , a lanthanide claim 1 , an actinide claim 1 , and mixtures thereof.3. The composition of claim 2 , wherein the transition metal is selected from the group consisting of cobalt claim 2 , copper claim 2 , zinc claim 2 , and mixtures thereof.4. The composition of claim 2 , wherein in Formulas (IV)-(VIII) claim 2 , each “D” is a donor atom that coordinates to a metal ion.5. The composition of claim 1 , wherein “J” in Formula (II) is an o- claim 1 , m- claim 1 , or p-xylene linker.6. The composition of claim 1 , wherein “Q” in Formula (III) is a 1 claim 1 ,3 claim 1 ,5-mesityl linker.7. The composition of claim 1 , wherein for each “E” in Formulas (IV)-(VIII) claim 1 , the sum of “a” plus “a′” is independently selected from 1 and 2.8. The composition of claim 1 , wherein for each “E” in Formulas (IV)-(VIII):the sum of all “a” plus “a′” for all of the “E”s in Formula (V) is about 5,the sum of all “a” plus “a′” for all of the “E”s in Formula (VI) is about 7, andthe sum of all “a” plus “a′” for all of the “E”s in Formula (VII) is about 9.9. The composition of claim 1 , wherein in Formulas (IV)-(VIII) claim 1 , at least one “R” is a benzyl group.10. The composition of claim 1 , wherein for each “G” is the moiety (CR) claim 1 , each “b” is an integer independently selected from about 0 to about 5 claim 1 , and wherein when “b” is 0 claim 1 , (CR)represents a covalent bond.11. The composition of claim 1 , further defined as having anti-microbial activity.12. The composition of claim 11 , wherein the anti-microbial activity is further defined as an anti-fungal activity.13Cryptococcus ...

NOSCAPINOID-PRODUCING MICROBES AND METHODS OF MAKING AND USING THE SAME

Engineered non-plant cells that produce a benzylisoquinoline alkaloid product that is a derivative of canadine along a metabolic pathway that converts canadine, or an analog of canadine, to a noscapinoid product are provided. Methods of culturing engineered non-plant cells that produce a noscapinoid product and pharmaceutical compositions are also provided. 1. An engineered non-plant cell that produces a benzylisoquinoline alkaloid product that is a derivative of canadine along a metabolic pathway that converts canadine , or an analog of canadine , to a noscapinoid product that comprises at least one compound that is selected from the group consisting of noscapinoids , precursors of noscapinoids , metabolites of noscapinoids , analogs of noscapinoids , intermediates of noscapinoids , and derivatives of noscapinoids , wherein an amount of the benzylisoquinoline alkaloid product that is produced in the engineered non-plant cell is more than the amount of the benzylisoquinoline alkaloid product that is produced in the non-plant cell.2. The engineered non-plant cell of claim 1 , wherein the engineered non-plant cell comprises one or more heterologous coding sequences encoding at least one enzyme involved in the metabolic pathway that converts canadine claim 1 , or an analog of canadine claim 1 , to a noscapinoid product.3. The engineered non-plant cell of claim 2 , wherein the engineered non-plant cell comprises heterologous coding sequences encoding more than one enzyme involved in the metabolic pathway that converts canadine claim 2 , or an analog of canadine claim 2 , to a noscapinoid product.4. The engineered non-plant cell of claim 3 , wherein the engineered non-plant cell comprises heterologous coding sequences encoding two distinct enzymes involved in the metabolic pathway that converts canadine claim 3 , or an analog of canadine claim 3 , to a noscapinoid product.5. The engineered non-plant cell of claim 3 , wherein the engineered non-plant cell comprises ...

1,3,6-dioxazocan-2-ones and antimicrobial cationic polycarbonates therefrom

Eight-membered ring cyclic carbonates comprising a ring nitrogen at position 6 (1,3,6-dioxazocan-2-ones) were prepared by reaction of precursor diols with active carbonates. The ring nitrogen is linked to a pendant group Y′ via a methylene linking group. The cyclic carbonates undergo organocatalyzed ring opening polymerization to form an initial polycarbonate comprising a backbone tertiary amine group. Quaternization of the initial polycarbonates forms cationic polycarbonates comprising a positive-charged backbone quaternary nitrogen. The cationic polycarbonates can be potent antimicrobial agents.

CRYSTAL FORM OF OZANIMOD HYDROCHLORIDE, AND PREPARATION METHOD THEREFOR

The present disclosure relates to crystalline form CS3 of ozanimod hydrochloride which can be used for treating autoimmune diseases, particularly used for preparing drugs for treating multiple sclerosis and ulcerative colitis and preparation method thereof. 1. A crystalline form CS3 of ozanimod hydrochloride , wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 19.6°±0.2° , 24.9°±0.2° and 5.8°±0.2° using CuKα radiation.2. The crystalline form CS3 of hydrochloride according to claim 1 , wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 7.8°±0.2° claim 1 , 11.7°±0.2° and 29.5°±0.2° using CuKα radiation.3. The crystalline form CS3 of hydrochloride according to claim 1 , wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 3.9°±0.2° claim 1 , 14.2°±0.2° and 20.7°±0.2° using CuKα radiation.4. A process for preparing crystalline form CS3 of hydrochloride according to claim 1 , wherein the process comprises: dissolving ozanimod hydrochloride into ethanol or a mixture of solvents selected from alcohols and arenes claim 1 , alcohols and nitriles claim 1 , alcohols and acids claim 1 , acids and water claim 1 , filtering and adding polymer into the solution and then evaporating at room temperature to obtain white solid.5. The process for preparing crystalline form CS3 of hydrochloride according to claim 4 , wherein said alcohols include methanol and ethanol; said acids include acetic acid; said arenes include toluene; said nitriles include acetonitrile.6. A pharmaceutical composition claim 1 , wherein said pharmaceutical composition comprises a therapeutically effective amount of crystalline form CS3 of hydrochloride according to and pharmaceutically acceptable carriers claim 1 , diluents or excipients.7. A method for preparing drugs of selective modulator of sphingosine-1-phosphate receptor claim 1 , comprising ...

ANTHELMINTIC DEPSIPEPTIDE COMPOUNDS

The present invention provides cyclic depsipeptide compounds of formula (I) and compositions comprising the compounds that are effective against parasites that harm animals, including humans. The compounds and compositions may be used for combating parasites in or on animals including mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in animals, including birds and mammals. 2. The anthelmintic cyclic depsipeptide of claim 1 , wherein{'sup': 1', '2', '1′', '2′, 'sub': 1', '3', '1', '3', '1', '3', '1', '3', '1', '3, '(e) Rand/or Rare each independently a 3- to 6-membered carbocyclic or 3- to 6-membered heterocyclic ring, or C-Calkyl or C-Chaloalkyl, wherein the C-Calkyl or C-Chaloalkyl is substituted by a 3- to 8-membered carbocyclic or 3- to 8-membered heterocyclic ring; wherein said 3- to 6-membered carbocyclic or 3- to 6-membered heterocyclic ring(s) or 3- to 8-membered carbocyclic or 3- to 8-membered heterocyclic ring(s) may be further independently substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and Rand/or Rare independently hydrogen or C-Calkyl; or'}{'sup': 1', '1′', '2', '2′, 'Rand Rtogether and/or Rand Rtogether independently form a 2-6-membered carbon chain to form a ring; and'}{'sup': 3', '3′', '4', '4′, 'sub': 1', '8, 'R, R, Rand Rare each independently hydrogen or C-Calkyl, optionally substituted by one or more halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino or dialkylamino; or'}{'sup': 1', '3', '1′', '3′, 'sub': 1', '3', '1', '3', '1', '3', '1', ...

A Method for Topically Treating Actinic Keratosis on the Scalp with Ingenol 3-(3,5-diethylisoxazole-4-carboxylate)

The invention relates to the treatment of actinic keratosis on the scalp with ingenol 3-(3,5-diethylisoxazole-4-carboxylate). 1. A method of treating a subject diagnosed with actinic keratosis on the scalp , said method comprising applying an effective amount of ingenol 3-(3 ,5-diethylisoxazole-4-carboxylate) to a treatment area on the scalp for three days.2. The method of claim 1 , wherein the method provides a reduction in the number of actinic keratosis lesions in the treatment area.3. The method of claim 1 , wherein the three day treatment is three consecutive days.4. The method of claim 1 , wherein the treatment area is up to about 250 cm.5. The method of claim 1 , wherein the effective amount of the ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate) is applied from a dosage strength formulation of ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate) of about 0.037%.6. The method of claim 1 , wherein the amount of the ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate) applied is about 0.9 mg ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate)/per day/250 cmtreatment area.7. The method of claim 1 , wherein the ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate) is formulated in a gel.8. The method of claim 1 , wherein the ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate) is topically applied in a concentration of about 0.037%.9. A method of treating a subject diagnosed with actinic keratosis on the scalp claim 1 , said method comprising topically applying an effective amount of ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate) to a treatment area on the the scalp for three consecutive days claim 1 , wherein said method provides a reduction in the number of actinic keratosis lesions in the treated area on the scalp claim 1 , wherein the treatment area is of a size up to about 250 cm claim 1 , and wherein the dosage strength of the ingenol 3-(3 claim 1 ,5-diethylisoxazole-4-carboxylate) is about 0.037%. The invention relates to the ...

NEW CATALYTIC SYSTEM FOR SCALABLE PREPARATION OF INDOXACARB

It is an object of the present invention to provide a novel and advantageous process for commercially preparing of indoxacarb which is racemic or enantiomerically enriched at chiral center from its amide precursor using a new catalytic system. 2. The process according to claim 1 , wherein the methoxycarbonylation agent is selected from the group consisting of methyl chloroformate claim 1 , dimethyl dicarbonate and the mixture thereof.3. The process according to claim 1 , wherein the metal salts of methylsulfinylmethylide is selected from the group consisting of alkali metals salts and/or the mixtures thereof.4. The process according to claim 3 , wherein the metal salt of methylsulfinylmethylide is selected from sodium methylsulfinylmethylide claim 3 , potassium methylsulfinylmethylide and/or the mixtures thereof.5. The process according to claim 1 , wherein the hydrocarbon solvent is selected from the group consisting of paraffinic solvents claim 1 , aromatic solvents and the mixtures thereof.6. The process according to claim 5 , wherein the hydrocarbon solvent is selected from the group consisting of hexane claim 5 , petroleum ether claim 5 , toluene claim 5 , chlorobenzene claim 5 , xylene claim 5 , mesitylene claim 5 , and the mixtures thereof.7. The process according to claim 1 , wherein the organic base is selected from the group consisting of secondary and/or tertiary amines and/or the mixture thereof.8. The process according to claim 7 , wherein the organic base is selected from the group consisting of N-methyl imidazole claim 7 , 4-dimethylaminopyridine claim 7 , 1 claim 7 ,4-diazabicyclo[2.2.2]octane (DABCO) claim 7 , 1 claim 7 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and/or the mixtures thereof.9. The process according to claim 8 , wherein the organic base is 4-dimethylaminopyridine.10. The process according to claim 1 , wherein the phase transfer catalyst is selected from the group consisting of tetra-butyl ammonium iodide claim 1 , tetra-ethyl ammonium ...

PHOTOCHROMIC HYDRAZONE SWITCHES

Provided herein are compounds for use as photochromic molecular switches having very long thermal isomerization half-lives and switchable fluorescence properties both in solution and the solid state. 2. The compound of claim 1 , wherein at least one of A or B is a group other than phenyl.3. The compound of claim 1 , wherein n+m is 4 or more.4. The compound of claim 1 , wherein n is 2 or m is 3.5. The compound of any one of - claim 1 , wherein each Rand Ris selected from the group consisting of heterocyclyl claim 1 , halo claim 1 , alkylamino claim 1 , dialkylamino claim 1 , diphenyl amino claim 1 , hydroxyl claim 1 , nitro claim 1 , cyano claim 1 , carboxyl claim 1 , carboxylalkyl and carboxamido.6. The compound of any one of - claim 1 , wherein A is selected from phenyl claim 1 , pyridine-2-yl claim 1 , naphth-2-yl claim 1 , naphth-1-yl claim 1 , quinolin-2-yl claim 1 , quinolin-8-yl claim 1 , or thien-2-yl.7. The compound of any one of - claim 1 , wherein (R)-A- is selected from 4-dialkylaminophenyl claim 1 , pyridine-2-yl claim 1 , naphth-2-yl claim 1 , naphth-1-yl claim 1 , 6-dialkylaminonaphth-2-yl claim 1 , thien-2-yl or 5(piperidin-1-yl)thien-2-yl.8. The compound of any one of - claim 1 , wherein B is selected from phenyl claim 1 , pyridine-2-yl claim 1 , naphth-2-yl claim 1 , naphth-1-yl claim 1 , quinolin-2-yl claim 1 , quinolin-8-yl claim 1 , or thien-2-yl.9. The compound of any one of - claim 1 , wherein (R)—B— is selected from 4-dialkylaminophenyl claim 1 , pyridine-2-yl claim 1 , naphth-2-yl claim 1 , naphth-1-yl claim 1 , 6-dialkylaminonaphth-2-yl claim 1 , quinolin-2-yl claim 1 , thien-2-yl or 5(piperidin-1-yl)thien-2-yl.10. The compound of any one of - claim 1 , wherein A and B are independently selected from phenyl claim 1 , pyridine-2-yl claim 1 , naphth-2-yl claim 1 , naphth-1-yl claim 1 , quinolin-2-yl or thien-2-yl.11. The compound of any one of - claim 1 , wherein (R)-A- is selected from 4-dialkylaminophenyl claim 1 , pyridine-2-yl claim 1 , ...

BAF Complex Modulating Compounds and Methods of Using the Same

The invention provided here creates a new paradigm for the treatment of a variety of conditions where modulation of a BAF complex is desired. The disclosure that follows outlines a strategy for modulating a BAF complex in a cell, and provides effective compounds, pharmaceutical compositions, development strategies, and treatment protocols, and describes many of the ensuing benefits. A new family of BAF complex modulating compounds has been developed based on a new chemical scaffold including a 12-membered macrolactam core structures. Contacting target cells in vitro or in vivo with the compounds and compositions of this invention can selectively inhibit the activity of BAF complexes in such cells. Some of the BAF complex modulating compounds in this family are particularly effective agents for treating cancer in conjunction with a ATR inhibitor. 4. The pharmaceutical composition of claim 1 , wherein Ris of the formula:{'br': None, 'sup': '1', '-L-Z (IC); or'}{'br': None, 'sup': 2', '3', '11, '-L-C(O)-L-R(ID)'}wherein:{'sup': '1', 'Lis an alkyl linker or a substituted alkyl linker;'}{'sup': 2', '3, 'Land Lare each independently selected from a covalent bond, an alkyl linker and a substituted alkyl linker;'}Z is heteroaryl-aryl, substituted heteroaryl-aryl, aryl-heteraryl or substituted heteroaryl-aryl; and{'sup': '11', 'sub': 3-10', '3-10', '3-10', '3-10, 'Ris alkyl, substituted alkyl, Ccycloalkyl, substituted Ccycloalkyl, Cheterocycle or substituted Cheterocycle.'}7. The pharmaceutical composition of claim 1 , wherein each of R claim 1 , R claim 1 , Rand Rare lower alkyl or substituted lower alkyl.12. A method of modulating a BAF complex in a cell claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting a cell comprising a BAF complex with a BAF complex modulating compound of to modulate the activity of a BAF complex in the cell.'}13. The method of claim 12 , wherein the cell is in vitro.14. A method of treating cancer claim 12 , ...

Compounds for inhibiting bacterial growth via phosphatidylglycerol binding

Antibacterial small molecule compounds, termed liptins, bind to phosphatidylglycerol in bacterial plasma membranes. The small molecule compounds comprise a three-dimensional complementary binding pocket for phosphatidylglycerol, disrupting membrane function in a bacteriostatic or bactericidal manner. Methods of inhibiting bacterial growth and/or treating Gram-positive or Gram-negative bacterial infection using such compounds are also disclosed.

Photo-coupled synergistically crosslinked hydrogel material and its composition, preparation method, use, product, and preparation kit

This invention provides a preparation, composition, product, and application of a photo-coupled synergistically crosslinked hydrogel material. The preparation includes dissolving Component A including a photosensitive polymer derivative having o-nitrobenzyl phototriggers and Component B including a polymer derivative having amine or alkene (double group) or sulfhydryl group in a biocompatible medium to obtain solution A and solution B, respectively; mixing the solution A and solution B homogeneously to obtain a hydrogel precursor solution; initiating photo-coupled synergistic crosslinking under an irradiation of a UV light to form the hydrogel. The irradiation causes the o-nitrobenzyl phototriggers to generate an aldehyde group/keto group or a nitroso group to initiate photo-coupled synergetic crosslinking. The photo-coupled synergistically crosslinked hydrogel has applications in tissue engineering, regenerative medicine, 3D printing and as a carrier of cell, protein or drug.

PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF PIMAVANSERIN

The present disclosure relates to novel, safe and efficient processes for the synthesis of Pimavanserin and salts thereof, as well as novel intermediates that can be used in these processes. 12. The process of claim 11 , wherein Ris an isobutoxy group.14. The process of claim 11 , wherein the compound of formula XIX is prepared by reacting a compound of formula XVIII with 1 claim 11 ,1′-carbonyldiimidazole. This application is a divisional of U.S. patent application Ser. No. 15/555,092, which is a U.S. national stage of International Patent Application No. PCT/US2016/020337, filed Mar. 2, 2016, which claims the benefit of U.S. Provisional Patent Application Nos. 62/126,840, filed Mar. 2, 2015; 62/161,421, filed May 14, 2015; 62/187,668, filed Jul. 1, 2015; 62/188,992, filed Jul. 6, 2015; 62/198,218, filed Jul. 29, 2015; and 62/270,310, filed Dec. 21, 2015, the entireties of which are incorporated by reference herein.The present disclosure relates to novel, safe and efficient processes for the synthesis of Pimavanserin and salts thereof, as well as novel intermediates that can be used in these processes.Pimavanserin tartrate, 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1-methylpiperidin-4-yl)urea L-hemi-tartrate, has the following chemical structure:Pimavanserin tartrate was developed by Acadia Pharmaceuticals and was approved under the trade name NUPLAZID® for use in patients with Parkinson's disease psychosis.Pimavanserin free base and its synthesis are disclosed in U.S. Pat. No. 7,601,740 (referred to herein as US '740 or the '740 patent) and U.S. Pat. No. 7,790,899 (referred to herein as US '899 or the '899 patent). US '740 discloses the synthesis of Pimavanserin free base (also referred to herein as “Compound A”), which includes O-alkylation followed by ester hydrolysis, and then in situ azidation. This process suffers from low process safety, and utilizes the hazardous reagent diphenylphosphoryl azide. The process is illustrated by the following Scheme 1.US ' ...

Matrix Metalloproteinase Inhibitors and Imaging Agents, And Methods Using Same

The present invention provides certain compounds, Formula (I), or salts or solvates thereof, which can be used as matrix metalloproteinase-targeted inhibitors or imaging agents. 3. The compound of claim 1 , wherein Ris present claim 1 , and wherein the compound further comprises a radioisotope-containing group claim 1 , wherein the radioisotope is bound to R.4. The compound of claim 3 , wherein the radioisotope is at least one selected from the group consisting of Tc claim 3 , F claim 3 , In claim 3 , Cu claim 3 , and Ga.6. A pharmaceutical composition comprising at least one compound of and further comprising at least one pharmaceutically acceptable carrier.7. A method of evaluating a subject's risk of developing a cardiovascular disease or disorder claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to a subject at least one compound of , wherein the at least one compound comprises a radioisotope or fluorophore,'}acquiring an image of at least a portion of the subject's body, andmeasuring the amount of compound bound to the imaged portion of the subject's body,wherein, if the measured amount of bound compound is above a determined control amount, the subject is diagnosed as having an increased risk of developing the cardiovascular disease or disorder.8. The method of claim 7 , wherein the subject is a mammal.9. The method of claim 8 , wherein the subject is a human.12. A pharmaceutical composition comprising at least one compound of and further comprising at least one pharmaceutically acceptable carrier.14. The method of claim 13 , wherein the disease or disorder is at least one selected from the group consisting of cancers claim 13 , inflammatory diseases claim 13 , cardiovascular diseases claim 13 , stroke claim 13 , aneurysm claim 13 , periodontitis claim 13 , hepatitis claim 13 , cirrhosis claim 13 , portal hypertension claim 13 , glomerulonephritis claim 13 , atherosclerosis claim 13 , emphysema claim 13 , asthma ...

1,3, 5-Dioxazine Derivatives, Method of Preparation and Application Thereof as Sulfide Scavenger

The present disclosure relates to 1,3,5-dioxazine derivatives of formula (I) capable of reducing or eliminating hydrogen sulfide and other objectionable sulfides from oil field produced hydrocarbon fluids such as petroleum, fuel oil, gasoline, diesel, liquid propane, liquid butane, an aquaculture and production/processing of syngas/natural gas. The present disclosure further provides a method for preparing 1,3,5-dioxazine derivatives of formula I, and a method for scavenging sulfur-based species including, but not limited to hydrogen sulfide or alkyl/aryl mercaptans from a medium. 3. A method for preparing the compound of formula I as claimed in claim 1 , wherein the method comprises reacting at least one amine compound with any or a combination of aqueous formaldehyde and paraformaldehyde under conditions effective to obtain the compound of formula I.4. The method according to claim 3 , wherein the at least amine compound is selected from any or a combination of 1 claim 3 ,2-diaminoethane claim 3 , 1 claim 3 ,3-Diaminopropane claim 3 , 1 claim 3 ,4-Diaminobutane claim 3 , 1 claim 3 ,4-Phenylenedimethanamine claim 3 , N claim 3 ,N-Bis(2-aminoethyl)-1 claim 3 ,2-ethanediamine claim 3 , Diethyl enetriamine claim 3 , triethylenetetramine claim 3 , polyalkylamines and derivatives thereof.5. The method according to claim 3 , wherein the any or a combination of aqueous formaldehyde and paraformaldehyde has a concentration ranging from 5 to 50%.6. The method according to claim 3 , wherein a molar ratio of the at least one amine compound to the any or a combination of aqueous formaldehyde and paraformaldehyde for one —NHgroup ranges from about 1:1 to about 1:20.7. A method for reducing hydrogen sulfide or alkyl/aryl mercaptan in a medium claim 1 , the method comprising contacting the hydrocarbon fluid with an effective amount of a compound of formula (I) according to .8. The method as claimed in claim 7 , wherein said medium is any of an oil field produced hydrocarbon fluid ...

Anthelmintic depsipeptide compounds

The present invention provides cyclic depsipeptide compounds of formula (I) wherein the stereochemical configuration of at least one carbon atom bearing the groups Cy 1 , Cy 2 , R 1 , R 2 , R 3 , R 4 , R a and R b is inverted compared with the naturally occurring cyclic depsipeptide PF1022A. The invention also provides compositions comprising the compounds that are effective against parasites that harm animals. The compounds and compositions may be used for combating parasites in or on mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in birds and mammals.

AN IMPROVED PROCESS FOR THE PREPARATION OF RALTEGRAVIR

The present invention provides a process for the preparation of crystalline anhydrous compound of Formula (X), Further, the present invention relates to the use of compound of Formula (X) preparation of Raltegravir (I) or its pharmaceutically acceptable salt thereof. 2. A process for the preparation of the crystalline anhydrous 2-(1-amino-1-methylethyl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1 ,6-dihydropyrimidine-4-carboxamide Formula (X) , (i) suspending or dissolving hydrated compound of Formula (X) in a solvent;', '(ii) removing the solvent to isolate crystalline anhydrous compound of Formula (X)., 'which comprises3. The process according to claim 2 , wherein the solvent used in step (i) is selected from the group comprising of aromatic hydrocarbon selected from toluene claim 2 , o-xylene claim 2 , p-xylene claim 2 , m-xylene; aliphatic hydrocarbon selected from hexane claim 2 , heptane; ketone selected from methyl isobutyl ketone (MIBK); ether selected from diethyl ether claim 2 , n-butyl ether or mixture thereof.5. The process according to claim 4 , wherein the amination step (i) is carried out in the presence of ammonia in a solvent selected from the group comprising of dichloromethane (DCM) claim 4 , tetrahydrofuron (THF) claim 4 , ethyl acetate claim 4 , acetone claim 4 , dimethyl formamide (DMF) claim 4 , acetonitrile claim 4 , dimethyl sulfoxide (DMSO) claim 4 , propylene carbonate or mixture thereof.6. The process according to claim 4 , wherein the step (ii) is carried out in the presence of a base selected from the group comprising of organic base or inorganic base claim 4 , in a solvent selected from the group comprising of dichloromethane claim 4 , toluene claim 4 , ethyl acetate claim 4 , water or mixture thereof.7. The process according to claim 4 , wherein the step (iii) is carried out in the presence of a base selected from the group comprising of alkali metal hydroxide selected from sodium hydroxide claim 4 , potassium hydroxide claim 4 , ...

COMPOUND HAVING SUBSTITUTED TRIPHENYLENE RING STRUCTURE, AND ORGANIC ELECTROLUMINESCENT DEVICE

An organic compound having an excellent electron injection and transport performance is provided as a material for a low-power-consumption organic electroluminescent device. A low-power-consumption organic electroluminescent device is also provided by using the compound. The compound is a compound of general formula () or () having a substituted bipyridyl and triphenylene ring structure. The organic electroluminescent device includes a pair of electrodes, and one or more organic layers sandwiched between the pair of electrodes, and uses the compound as constituent material of at least one of the organic layers. 610-. (canceled) The present invention relates to compounds suited for an organic electroluminescent device (hereinafter, simply referred to as “organic EL device”), a preferred self light-emitting device for various display devices, and to the device. Specifically, the invention relates to compounds having a substituted bipyridyl and triphenylene ring structure, and to organic EL devices that use the compounds.The organic EL device is a self-emitting device, and has been actively studied for their brighter, superior viewability and ability to display clearer images compared with the liquid crystal device.In 1987, C. W. Tang et al, at Eastman Kodak developed a lamina-ted structure device using materials assigned with different roles, realizing practical applications of an organic EL device with organic materials. These researchers laminated an electron-transporting phosphor and a hole-transporting organic material, and injected both the charges into the phosphor layer to cause emission in order to obtain a high luminance of 1,000 cd/mor more at a voltage of 10 V or less (refer to Patent Documents 1 and 2, for example).To date, various improvements have been made for practical applications of the organic EL device. In order to realize high efficiency and durability, various roles are further subdivided to provide an electroluminescent device that includes an ...

PET PROBES OF RADIOFLUORINATED CARBOXIMIDAMIDES FOR IDO-TARGETED IMAGING

F labeled IDO1 imaging constructs are constructed for positron emission tomography (PET). Synthetic methodology involves the coupling of a 1-fluoro-2-halo-4-aminobenzene and a 4-amino-N-hydroxy-1,2,5-oxadiazole-3-carboximidoyl chloride wherein at least one of the coupled compounds comprises an F. The F labeled IDO1 imaging constructs are useful for imaging cancer cells in a patient. 4. The method according to claim 3 , wherein providing a 4-amino-N-hydroxy-1 claim 3 ,2 claim 3 ,5-oxadiazole-3-carboximidoyl chloride comprises:providing a 2-halo-N,N,N-trimethyl-4-nitrobenzenaminium trifluoromethanesulfonate;combining the 2-halo-N,N,N-trimethyl-4-nitrobenzenaminium trifluoromethanesulfonate with cryptated potassium fluoride in an organic solvent to form a 1-fluoro-2-halo-4-nitrobenzene;{'sub': '4', 'combining the 1-fluoro-2-halo-4-nitrobenzene with NaBHand a Pd/C catalyst in an organic solvent to form the 1-fluoro-2-halo-4-aminobenzene.'}5. A method of performing positron emission tomography (PET) claim 1 , comprising injecting a solution comprising an F labeled IDO1 imaging construct according to into a patient suspected of having cancer.7. The method according to claim 5 , wherein the cancer is breast cancer.8. The method according to claim 5 , further comprising administering a treatment for the cancer to the patient before claim 5 , during claim 5 , or after injecting the solution.9. The method according to claim 8 , wherein the treatment comprises administration of surgery claim 8 , radiation claim 8 , chemotherapy claim 8 , immunotherapy claim 8 , or a combination of two or more of the foregoing.10. The method according to claim 8 , wherein the cancer is one in which indoleamine 2 claim 8 ,3-dioxygenase-1 (IDO1) is over-expressed relative to normal tissue.11. The method according to claim 8 , wherein the treatment comprises administering an inhibitor of indoleamine 2 claim 8 ,3-dioxygenase-1 (IDO1) to the patient.12. The method according to claim 8 , wherein the ...

CREATINE PRODRUGS, COMPOSITIONS AND METHODS OF USE THEREOF

The invention describes membrane permeable creatine prodrugs, pharmaceutical compositions comprising membrane permeable creatine prodrugs, and methods of treating diseases such as ischemia, heart failure, neurodegenerative disorders and genetic disorders affecting the creatine kinase system comprising administering creatine prodrugs or pharmaceutical compositions thereof. The invention also describes treating a genetic disease affecting the creatine kinase system, such as, for example, a creatine transporter disorder or a creatine synthesis disorder comprising administering creatine prodrugs or pharmaceutical compositions thereof. 134.-. (canceled)36. The compound of claim 35 , wherein Ris hydrogen claim 35 , —OR claim 35 , —C(O)OR claim 35 , or —C(O)R.37. The compound of claim 35 , wherein Ris hydrogen claim 35 , methyl claim 35 , ethyl claim 35 , n-propyl claim 35 , isopropyl claim 35 , dodecyl claim 35 , tert-butyl claim 35 , phenyl or cyclohexy.38. The compound of claim 35 , wherein each R claim 35 , R claim 35 , R claim 35 , Rand Ris independently Calkyl claim 35 , substituted Calkyl claim 35 , Ccycloalkyl claim 35 , substituted Ccycloalkyl claim 35 , Caryl or substituted Caryl.39. The compound of claim 35 , wherein each R claim 35 , R claim 35 , Rand Ris independently hydrogen claim 35 , methyl claim 35 , ethyl claim 35 , n-propyl claim 35 , isopropyl claim 35 , dodecyl claim 35 , tert-butyl claim 35 , phenyl or cyclohexyl.40. The compound of claim 35 , wherein Rand Rare each independently —ORor —C(O)R.41. The compound of claim 35 , wherein the substituted Calkyl claim 35 , substituted Cheteroalkyl claim 35 , substituted Ccycloalkyl claim 35 , substituted Ccycloalkylalkyl claim 35 , substituted Cheterocycloalkylalkyl claim 35 , substituted Caryl claim 35 , substituted Cheteroaryl claim 35 , substituted Carylalkyl claim 35 , substituted Cheteroarylalkyl claim 35 , or substituted Ccycloalkyl claim 35 , is Calkyl claim 35 , Cheteroalkyl claim 35 , Ccycloalkyl ...

METHOD FOR PRODUCING LACTAM COMPOUND, AND LACTAM COMPOUND PRODUCED THEREBY

The present invention relates to a method for producing a lactam compound from dioxazolone in the presence of a catalyst having a particular ligand, and to a lactam compound produced thereby, and can produce a lactam compound with excellent selectivity and an excellent yield by using the combination of a starting material having a particular functional group and a particular catalyst having a particular ligand. 6. The method of preparing a lactam compound of claim 1 , wherein the catalyst is used at 0.01 to 0.1 mol with respect to 1 mol of the 3-substituted dioxazol-one compound.7. The method of preparing a lactam compound of claim 1 , wherein the base is one or two or more selected from NaBAr claim 1 , AgSbF claim 1 , AgNTf claim 1 , AgBF claim 1 , AgPF claim 1 , AgOTf claim 1 , and AgOAc.8. The method of preparing a lactam compound of claim 1 , wherein the base is used at 0.01 to 0.1 mol with respect to 1 mol of the 3-substituted dioxazol-one compound.9. The method of preparing a lactam compound of claim 1 , wherein the amidating is performed at 20 to 80° C.10. The method of preparing a lactam compound of claim 1 , wherein in Chemical Formula 1 claim 1 , M is iridium claim 1 , X is chloro claim 1 , Rto Rare independently of one another (C1-C30)alkyl claim 1 , Ris a halogen claim 1 , and n is an integer of 0 to 2.11. The method of preparing a lactam compound of claim 2 , wherein{'sub': a1', 'a2, 'Rand Rare independently of each other hydrogen, (C6-C20)aryl, or phthalimido;'}{'sub': a3', 'a6, 'Rto Rare independently of one another hydrogen, a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, or (C1-C20)alkoxy, or may be connected to an adjacent substituent to form an aromatic ring with or without a fused ring; and'}q is an integer of 1 or 2.12. The method of preparing a lactam compound of claim 3 , wherein{'sub': a1', 'a2, 'Rand Rare independently of each other hydrogen or phthalimido;'}{'sub': a7', 'a10, 'Rto Rare independently of one another hydrogen, a halogen, (C1-C20) ...

CREATINE PRODRUGS, COMPOSITIONS AND METHODS OF USE THEREOF

The invention describes membrane permeable creatine prodrugs, pharmaceutical compositions comprising membrane permeable creatine prodrugs, and methods of treating diseases such as ischemia, heart failure, neurodegenerative disorders and genetic disorders affecting the creatine kinase system comprising administering creatine prodrugs or pharmaceutical compositions thereof. The invention also describes treating a genetic disease affecting the creatine kinase system, such as, for example, a creatine transporter disorder or a creatine synthesis disorder comprising administering creatine prodrugs or pharmaceutical compositions thereof. 134.-. (canceled)36. The compound of claim 35 , wherein Ris hydrogen claim 35 , methyl claim 35 , ethyl claim 35 , n-propyl claim 35 , isopropyl claim 35 , dodecyl claim 35 , tert-butyl claim 35 , phenyl or cyclohexyl.37. The compound of claim 35 , wherein each R claim 35 , R claim 35 , and Ris independently Calkyl claim 35 , substituted Calkyl claim 35 , Ccycloalkyl claim 35 , substituted Ccycloalkyl claim 35 , Caryl or substituted Caryl.38. The compound of claim 35 , wherein each R claim 35 , Rand Ris independently hydrogen claim 35 , methyl claim 35 , ethyl claim 35 , n-propyl claim 35 , isopropyl claim 35 , dodecyl claim 35 , tert-butyl claim 35 , phenyl or cyclohexyl.39. The compound of claim 35 , wherein Rand Rare each independently —ORor —C(O)R.40. The compound of claim 35 , wherein the substituted Calkyl claim 35 , substituted Cheteroalkyl claim 35 , substituted Ccycloalkyl claim 35 , substituted Ccycloalkylalkyl claim 35 , substituted Cheterocycloalkylalkyl claim 35 , substituted Caryl claim 35 , substituted Cheteroaryl claim 35 , substituted Carylalkyl claim 35 , substituted Cheteroarylalkyl claim 35 , or substituted Ccycloalkyl claim 35 , is Calkyl claim 35 , Cheteroalkyl claim 35 , Ccycloalkyl claim 35 , Ccycloalkylalkyl claim 35 , Cheterocycloalkylalkyl claim 35 , substituted Caryl claim 35 , Cheteroaryl claim 35 , Carylalkyl ...

HIV REPLICATION INHIBITOR

The present invention provides a novel compound having an antiviral activity, in particular, an HIV replication inhibiting activity, as well as a pharmaceutical composition, in particular, an anti-HIV agent. 2: The compound according to or its pharmaceutically acceptable salt claim 1 , wherein Ris a hydrogen atom.3: The compound according to claim 1 , or its pharmaceutically acceptable salt claim 1 , wherein n is 1.4: The compound according to or its pharmaceutically acceptable salt claim 3 , wherein Ris substituted or unsubstituted alkyloxy claim 3 , or substituted or unsubstituted cycloalkyloxy.5: The compound according to or its pharmaceutically acceptable salt claim 1 , wherein ring A is monocyclic aromatic carbocycle claim 1 , monocyclic non-aromatic carbocycle claim 1 , monocyclic aromatic heterocycle or monocyclic non-aromatic heterocycle claim 1 ,{'sup': 'A', 'wherein the ring may be fused with another aromatic carbocycle, non-aromatic carbocycle, aromatic heterocycle, or non-aromatic heterocycle; the ring may form a spiro ring together with another aromatic carbocycle, non-aromatic carbocycle, aromatic heterocycle or non-aromatic heterocycle; two atoms constituting ring A which are not adjacent to each other may be cross-linked with alkylene, alkenylene or alkynylene; and/or, rings may be substituted with one or more of R;'}{'sup': A', 'A', 'A1, 'wherein Ris each independently, halogen, cyano, nitro, oxo, azide, trimethylsilyl or —X—R;'}{'sup': A', 'A2', 'A2', 'A2', 'A2', 'A2', 'A2', 'A2', 'A2', 'A2', 'A2', 'A3', 'A2', 'A2, 'sub': 2', '2', '2, 'Xis a single bond, —O—, —S—, —NR—, ═N—, —CO—, —SO—, —O—CO—, —CO—O—, —NR—CO—, —CO—NR—, —NR—CO—O—, —CO—O—NR—, —O—CO—NR—, —NR—O—CO—, —CO—NR—O—, —O—NR—CO—, —NR—CO—NR—, —NR—SO— or —SO—NR—;'}{'sup': A1', 'A', 'A1, 'Ris a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclyl, substituted or ...

ANTHELMINTIC DEPSIPEPTIDE COMPOUNDS

The present invention provides cyclic depsipeptide compounds of formula (I) and compositions comprising the compounds that are effective against parasites that harm animals. The compounds and compositions may be used for combating parasites in or on mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in birds and mammals. 2. The anthelmintic cyclic depsipeptide of claim 1 , wherein{'sup': 1', '3, 'sub': 1', '8, '(f) Rand Rare each independently C-Calkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and'}{'sup': 2', '4, 'sub': 1', '8, 'Rand Rare each independently C-Calkyl; or'}{'sup': 2', '4, 'sub': 1', '8, '(h) Rand Rare each independently C-Calkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and'}{'sup': 1', '3, 'sub': 1', '8, 'Rand Rare each independently C-Calkyl; or'}{'sup': 1', '2, 'sub': 1', '8, '(e) Rand Rare each independently C-Calkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and'}{'sup': 3', '4, 'sub': 1', '8, 'Rand Rare each independently C-Calkyl; or'}{'sup': 1', '4, 'sub': 1', '8, '(g) Rand Rare each independently C-Calkyl substituted by one or more substituents selected from the group consisting of aryl, ...

ANTHELMINTIC DEPSIPEPTIDE COMPOUNDS

The present invention provides cyclic depsipeptide compounds of formula (I) and compositions comprising the compounds that are effective against parasites that harm animals. The compounds and compositions may be used for combating parasites in or on mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in birds and mammals. 2. (canceled)3. The anthelmintic cyclic depsipeptide of claim 1 , wherein{'sub': 1', '8, '(a) R is C-Calkyl substituted by one or more halogen; and'}{'sup': 2', '3', '4, 'sub': 1', '8, 'R, Rand Rare each independently C-Calkyl; or'}{'sup': '2', 'sub': 1', '8, '(b) Ris C-Calkyl substituted by one or more halogen; and'}{'sup': 1', '3', '4, 'sub': 1', '8, 'R, Rand Rare each independently C-Calkyl; or'}{'sup': '3', 'sub': 1', '8, '(c) Ris C-Calkyl substituted by one or more; and'}{'sup': 1', '2', '4, 'sub': 1', '8, 'R, Rand Rare each independently C-Calkyl; or'}{'sup': '4', 'sub': 1', '8, '(d) Ris C-Calkyl substituted by one or more; and'}{'sup': 1', '2', '3, 'sub': 1', '8, 'R, Rand Rare each independently C-Calkyl.'}4. (canceled)5. (canceled)6. (canceled)7. The anthelmintic cyclic depsipeptide of claim 3 , wherein one of R claim 3 , R claim 3 , Rand Ris C-C-alkyl substituted by halogen.8. The anthelmintic cyclic depsipeptide of claim 3 , wherein Ris C-Calkyl substituted by halogen.9. The anthelmintic cyclic depsipeptide of claim 3 , wherein Ris C-Calkyl substituted by halogen.10. The anthelmintic cyclic depsipeptide of claim 3 , wherein Ris C-Calkyl substituted by halogen.11. The anthelmintic cyclic depsipeptide of claim 3 , wherein Ris C-Calkyl substituted by halogen.12. (canceled)13. The anthelmintic cyclic depsipeptide of claim 3 , wherein halogen is fluoro.15. The anthelmintic cyclic depsipeptide of claim 14 , wherein:{'sup': 1A', '1B', '1C, 'Ris fluoro or trifluoromethyl Rand Rare independently hydrogen or methyl; and'}{'sup': 1D', '1E, 'Rand Rare independently ...

METHODS FOR IDENTIFYING INHIBITORS OF "STIMULATOR OF INTERFERON GENE"- DEPENDENT INTERFERON PRODUCTION

The present invention relates to the use cyclic-di-nucleotide and related scaffold molecules that measurably inhibit STING signaling, and methods for their use in identifying more potent inhibitors of STING signaling. In particular, the methods provided can be used to identify potent inhibitors of STING signaling, which are useful in the treatment of autoimmune and inflammatory diseases. Also provided are compounds having STING inhibitory activity useful in the treatment of autoimmune and inflammatory diseases. 2. The scaffold molecule according to claim 1 , wherein the scaffold molecule measurably binds to one or more of wild type hSTING claim 1 , hSTING HAQ allele claim 1 , or hSTING REF allele.3. The scaffold molecule according to claim 2 , wherein binding to hSTING is measured by Tshift in a differential scanning fluorometry assay.4. The scaffold molecule according to claim 3 , wherein the Tshift is measured according to the assay of Example 11 claim 3 , and the Tshift is in the range of about 2 to about 15° C. for WT hSTING or hSTING REF allele and in the range of about 2 to about 25° C. for hSTING HAQ allele.5. The scaffold molecule according to claim 1 , wherein the measurable STING inhibitory activity is measured in a competition assay with a STING agonist.6. The scaffold molecule according to claim 5 , wherein the STING agonist is 2′3′-RR-(A)(A).7. The scaffold molecule according to claim 5 , wherein the scaffold molecule has an IC50 in the competition assay of less than 10 mM.8. The scaffold molecule according to claim 5 , wherein the scaffold molecule has an IC50 in the competition assay of less than 5 mM.9. The scaffold molecule according to claim 5 , wherein the scaffold molecule has an IC50 in the competition assay in the range of 100 μM to 5 μM.10. (canceled)11. The scaffold molecule according to wherein Xand Xare —SH.15. A method of identifying a STING inhibitor comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) providing a ...

DIHYDROOXADIAZINONES

The present invention provides dihydrooxydiazinone compounds of general formula (I): in which R, R, R, and R, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients. 2. The compound according to claim 1 , where{'sup': '1', 'sub': 1', '3', '1', '3', '1', '3, 'Ris selected from a hydrogen atom, a halogen atom, a cyano group, a C-C-alkyl group, a C-C-haloalkyl group, and a C-C-haloalkoxy group;'}{'sup': '2', 'Ris selected from a hydrogen atom and a halogen atom;'}{'sup': '3', 'claim-text': [{'sub': 1', '6', '1', '4, 'a C-C-alkyl group which is optionally substituted with a substituent which is selected from a hydroxy group, a C-C-alkoxy group, and a 3- to 7-membered heterocycloalkyl group;'}, {'sub': 2', '6', '1', '4, 'a C-C-alkenyl group which is optionally substituted with an C-C-alkoxy group;'}, {'sub': 3', '7, 'a C-C-cycloalkyl group, which is optionally substituted with a hydroxy group;'}, {'sub': 5', '7, 'a C-C-cycloalkenyl group, which is optionally substituted with a hydroxy group;'}, {'sub': '2', 'sup': '9', 'claim-text': and said heterocycloalkyl group is optionally substituted with one, or two substituents and each substituent is independently selected from', 'a halogen atom;', 'a cyano group;', 'a hydroxy group;', {'sub': 1', '3, 'a C-C-alkyl group which is optionally further substituted with a hydroxy group;'}, {'sub': 1', '3, 'a C-C-alkoxy group;'}, {'sup': 5', '6, 'a C(O)NRRgroup and'}, {'sup': 5', '6, 'a NRRgroup;'}], 'a 3- to 7-membered-heterocycloalkyl group, comprising one, or two heteroatoms which are independently selected from —O—, S(O), and —NR—,'}, {'sup': '9', 'sub': 1', '3, 'a 5- to ...

CONJUGATED OLIGOMER-BASED MACROCYCLES FOR LIVE CELL IMAGING

A phenyleneethynylene macrocycle (PEMC) is constructed that is a cyclic or polycyclic oligo (oligophenyleneethynylene-co-polyamine) where a monodispersed oligophenyleneethynylene is coupled with a polyamine. The PEMC is formed by coupling a monodispersed di-aldehyde end-capped oligophenyleneethynylene with a polyamine to form a macrocyclic imine and reducing the imine to an amine. The PEMC is useful at entering living cells for the fluorescence imaging of the living cells without toxicity to the cells. 1. A phenyleneethynylene macrocycle (PEMC) , comprising a cyclic or polycyclic oligo (oligophenyleneethynylene-co-polyamine) where the polyamine is a diamine , triamine or tetraamine , where the oligophenyleneethynylene is a monodispersed dimer , trimer , tetramer , or pentamer.6. The PEMC according to claim 1 , wherein the cyclic oligo (oligophenyleneethynylene-co-polyamine) is a unimacrocycle (2/1).7. The PEMC according to claim 1 , wherein the polycyclic oligo (oligophenyleneethynylene-co-polyamine) is a trimacrocycle (3/3); a tetramacrocycle (3/6); a tetramacrocycle (4/4); or a hexamacrocycle (4/6).9. The PEMC according to claim 1 , wherein the amines of the cyclic oligo (oligophenyleneethynylene-co-polyamine) are in the form of an ammonium ion paired with an anion.10. The PEMC according to claim 9 , wherein the anion is a trifluoroacetate claim 9 , acetate claim 9 , or a halide.11. A method of preparing a PEMC according to claim 1 , comprising:providing a monodispersed di-aldehyde end-capped oligophenyleneethynylene;providing a polyamine;combining the monodispersed di-aldehyde end-capped oligophenyleneethynylene with the polyamine to form a macrocyclic imine;reducing the imine to an amine to form a cyclic or polycyclic oligo (oligophenyleneethynylene-co-polyamine).16. The method according to claim 11 , wherein the reducing comprises combining with NaBH.17. The method according to claim 11 , further comprising protonating with an acid.18. The method according to ...

Calpain modulators and therapeutic uses thereof

Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to macrocyclic α-keto amide derivatives and their use as therapeutic agents.

Oxo-heterocyclic substituted carboxylic acid derivates and the use thereof

The present invention relates to novel carboxylic acid derivates of the formula (I), having an oxo-substituted azaheterocyclic partial structure, method for the production thereof, use thereof for treating and/or preventing illnesses and use thereof for producing medications for treating and/or preventing illnesses, particularly for treating and/or preventing cardiovascular diseases. The compounds act as activators of soluble guanylate cyclase.

Oxo-heterocyclically substituted alkyl carboxylic acids and use thereof

The present application relates to novel alkyl carboxylic acids, having an oxo-substituted aza-heterocyclical partial structure, to a method for producing same, to the use thereof for treating and/or preventing disease, and to the use thereof for formulating pharmaceutical products for treating and/or preventing disease, in particular for treating and/or preventing cardiovascular conditions.

Catalyst systems based on macrocyclic ligands

The present invention discloses the use of rotoxane ligands to prepare catalyst systems suitable for the oligomerisation or polymerisation of ethylene and alpha-olefins.

Di-macrocycles

NEW ANTICANCER COMPOUNDS

Calpain modulators and therapeutic uses thereof

Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to macrocyclic α-keto amide derivatives and their use as therapeutic agents.