- HETEROCYCLIC GLP-1 AGONISTS
-
This disclosure relates to GLP-1 agonists of Formula (I), including pharmaceutically acceptable salts and solvates thereof, and pharmaceutical compositions including the same.
- -
-
Page/Page column 248-249
(2022/02/15)
-
- Compounds and methods of use
-
Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X1, X2, X3, X4, Y, A, L1, L2, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
- -
-
Page/Page column 572; 573
(2021/08/04)
-
- Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency
-
Non-covalent inhibitors of the main protease (Mpro) of SARS-CoV-2 having a pyridinone core were previously reported with IC50 values as low as 0.018 μM for inhibition of enzymatic activity and EC50 values as low as 0.8 μM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of Mpro and N-methylation of a uracil ring. Free energy perturbation calculations provided guidance on the choice of the heterocycles, and protein crystallography confirmed the desired S4 placement. Here we report inhibitors with EC50 values as low as 0.080 μM, while remdesivir yields values of 0.5-2 μM in side-by-side testing with infectious SARS-CoV-2. A key factor in the improvement is enhanced cell permeability, as reflected in PAMPA measurements. Compounds 19 and 21 are particularly promising as potential therapies for COVID-19, featuring IC50 values of 0.044-0.061 μM, EC50 values of ca. 0.1 μM, good aqueous solubility, and no cytotoxicity.
- Zhang, Chun-Hui,Spasov, Krasimir A.,Reilly, Raquel A.,Hollander, Klarissa,Stone, Elizabeth A.,Ippolito, Joseph A.,Liosi, Maria-Elena,Deshmukh, Maya G.,Tirado-Rives, Julian,Zhang, Shuo,Liang, Zhuobin,Miller, Scott J.,Isaacs, Farren,Lindenbach, Brett D.,Anderson, Karen S.,Jorgensen, William L.
-
supporting information
p. 1325 - 1332
(2021/08/06)
-
- MACROCYCLIC FUSED PYRRAZOLES AS MCL-1 INHIBITORS
-
Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R 1a, R 1b, L 1, L 2, L 3, X, A, B and C are as defined as set forth
- -
-
Paragraph 0963
(2020/08/13)
-
- 3-(AZOLYLMETHOXY)BIPHENYL DERIVATIVES AS INHIBITORS OF THE PD-1/PD-L1 PROTEIN/PROTEIN INTERACTION
-
The present invention provides novel compounds of formula (I) that are useful as inhibitors of the PD-1/PD-L1 protein/protein interaction. The compounds may be used in the treatment of cancer, infectious diseases and neurodegenerative diseases such as schizophrenia, Alzheimer, multiple sclerosis or Parkinson.
- -
-
Page/Page column 39-41
(2019/01/22)
-
- Versatile Photochemical Reactivity of Diverse Substituted 2-, 4- and 5-(o-Vinylstyryl)oxazoles
-
To study the effects of the position of the hexatrienyl moiety on the oxazole ring, novel substituted cis/trans-2/4/5-(2-vinylstyryl)oxazoles have been synthesized. These novel compounds were prepared by Wittig reaction from the diphosphonium salt of α,α′-o-xylenedibromide, formaldehyde and the corresponding 2-methyl-4-, 4-methyl-2-, 2-pheny-5- and 4-methyl-5-oxazolecarbaldehyde, respectively. Aldehydes were synthesized by using several synthetic approaches. By applying intramolecular photocycloaddition, 2-methyl-4-(2-vinylstyryl)oxazole afforded, as major product, fused oxazoline-benzobicyclo[3.2.1]octene with small quantities of 4-(1,2-dihydronaphthalen-2-yl)-2-methyloxazole, as electrocyclization product. Upon irradiation of 4-methyl-5-(2-vinylstyryl)oxazole, endo- and exo-benzobicyclo[2.1.1]hexene products were formed by [2+2] cycloaddition; this was the first instance of the 1,4-closure to the bicyclo[2.1.1]hexene skeleton in the 2-, 4-, and 5-oxazole-stilbene derivatives studied so far. Derivatives 2-phenyl-5- and 4-methyl-2-(2-vinylstyryl)oxazole did not react and gave only high-weight molecular products but were crucial as a comparison in the overall mechanistic study. We have found that, depending on the position of the hexatrienyl moiety in the oxazole ring, as well as on the position of the methyl/phenyl substituents, these new vinylstyryl-2/4/5-oxazole derivatives show diverse photochemical behavior.
- ?agud, Ivana,?indler-Kulyk, Marija,Vojnovi?-Jandri?, Dragana,Marini?, ?eljko
-
p. 515 - 524
(2018/02/09)
-
- SUBSTITUTED THIAZOLE OR OXAZOLE P2X7 RECEPTOR ANTAGONISTS
-
The present invention refers to novel substituted thiazole and oxazole compounds of formula (I) having P2X7 receptor (P2X7) antagonistic properties. The compounds are useful in the treatment or prophylaxis of diseases associated with P2X7 receptor activity in animals, in particular humans.
- -
-
Page/Page column 36
(2015/09/22)
-
- PYRAZOLE COMPOUNDS AND USE THEREOF
-
The pyrazole compound of the present invention is represented by the following general formula (I). The pyrazole compound of the present invention or a salt thereof or a solvate thereof potently inhibits liver glycogen phosphorylase, and, therefore, is useful as a therapeutic or prophylactic agent for diabetes. wherein each symbol denotes as described in the specifications.
- -
-
Page/Page column 44
(2009/05/29)
-
- INTEGRASE INHIBITORS 3
-
The present invention provides a method of treatment or prophylaxis of a viral infection in a subject comprising administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative, salt or prodrug thereof. Compounds of formula (I) are also provided.
- -
-
Page/Page column 62
(2008/06/13)
-
- Synthesis of oxazolyl-substituted morpholinium salts
-
Morpholinium salts coupled to oxazolyl moieties have been synthesized via nucleophilic substitution of a series of oxazolyl chlorides with morpholine. The oxazole moieties were first synthesized and then coupled with morpholine. The corresponding hydrochloride and methyl iodide salts were obtained, purified, characterized and then tested for muscarinic receptor binding affinity. Biological test results from MDS Pharma Services revealed no significant muscarinic receptor affinity.
- Boulos, John,Stujenske, Christina
-
p. 443 - 445
(2007/10/03)
-
- Cephalosporin derivatives and processes for the preparation thereof
-
PCT No. PCT/KR96/00255 Sec. 371 Date Jun. 26, 1998 Sec. 102(e) Date Jun. 26, 1998 PCT Filed Dec. 27, 1996 PCT Pub. No. WO97/24359 PCT Pub. Date Jul. 10, 1997The invention provides novel cephalosporin derivatives of the formula (I) and salts thereof for use in pharmaceutical compositions. Also novel precursors for synthesis of the cephalosporins are disclosed.
- -
-
-
- Synthesis of oxazolyl- and furanyl-substituted imidazole hydrochlorides and methiodides
-
Oxazolyl-5- and furanyl-2-substituted imidazoles have been synthesized by coupling the two ring systems via the dipolar cycloadditon of tosyl methyl isocyanide to the corresponding oxazolyl and furanyl aldimines in basic media. These substitute oxazolyl and furanylimidazole bases obtained in this manner were then subjected to hydrogen chloride gas and to methyl iodide to form the corresponding hydrochlorides and methyliodides, respectively. All compounds were purified, characterized and then tested for muscarinic binding affinity. Biological test results revealed low muscarinic receptor affinity and selectivity.
- Boulos, John,Schulman, Jerome
-
p. 859 - 863
(2007/10/03)
-