- Design of iodinated radioligands for SPECT imaging of central human 5-HT4R using a ligand lipophilicity efficiency approach
-
A series of iodinated ligands for the SPECT imaging of 5-HT4 receptors was designed starting from the previously reported hit MR-26132. We focused on the modulation of the piperidine-containing lateral chain by introducing hydrophilic groups in order to decrease the liphophilicity of the new ligands. All the synthesized compounds were tested for their binding affinities on 5-HT4Rs and based on the Ligand Lipophilicity Efficiency approach, compound 13 was further selected for radioiodination with iodine-125 and imaging experiments. Compound 13 showed its ability to displace the specific signal of the reference compound [125I]SB-207710 but no significant detection of [125I]13 was observed in vivo in SPECT experiments.
- Babin, Victor,Bouillon, Jean-Philippe,Cailly, Thomas,Davis, Audrey,Dubost, Emmanuelle,Fabis, Frédéric,Lohier, Jean-Fran?ois,Millet, Philippe,Pigrée, Gilbert,Reboul, Vincent,Tournier, Benjamin B.
-
-
- AMINO-QUINOLINES AS KINASE INHIBITORS
-
Disclosed are compounds having the formula:wherein R 1 , R 2 , R 3 and Z are as defined herein, and methods of making and using the same.
- -
-
Page/Page column 59
(2018/06/22)
-
- NON-FUSED TRICYCLIC COMPOUNDS
-
Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.
- -
-
Paragraph 00515
(2018/11/26)
-
- ANTI-BACTERIAL COMPOUNDS
-
A compound of Formula (II): for use in the prevention or treatment of a bacterial infection.
- -
-
Page/Page column 114
(2017/06/28)
-
- AMINO-QUINOLINES AS KINASE INHIBITORS
-
Disclosed are compounds having the formula: wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.
- -
-
Page/Page column 68; 69
(2018/05/15)
-
- OXYSTEROLS AND METHODS OF USE THEREOF
-
Compounds are provided according to Formula (I), and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein A, R1, and R5 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
- -
-
Paragraph 00136
(2017/10/31)
-
- AMINO-QUINOLINES AS KINASE INHIBITORS
-
Disclosed are compounds having the formula: wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.
- -
-
Paragraph 0128
(2016/10/31)
-
- TRIAZOLYL DERIVATIVES AS SYK INHIBITORS
-
Provided are triazole derivatives of Formula I which are potent inhibitors of spleen tyrosine kinase and pharmaceutical composition. The triazole derivatives are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.
- -
-
Page/Page column 90
(2014/04/17)
-
- FURO[3,4-C]QUINOLINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION
-
The present invention relates to compounds defined by formula (I), wherein the variables R1-R8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol
- -
-
Page/Page column 46; 47
(2013/03/26)
-
- Furo[3,4-c]quinoline derivatives, medicaments containing such compounds, their use and process for their preparation
-
The present invention relates to compounds defined by formula I wherein the variables R1-R8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol es
- -
-
Paragraph 0269-0272
(2013/08/28)
-
- TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION
-
The present invention relates to compounds defined by formula I wherein the variables R1-R8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol ester transfer protein (CETP) and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme.
- -
-
Page/Page column 178
(2012/03/10)
-
- PHENYL-HETEROARYL AMINE COMPOUNDS AND THEIR USES
-
The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I, and pharmaceutical compositions comprising such compounds
- -
-
Page/Page column 83
(2012/06/01)
-
- 3-(AMINOARYL)-PYRIDINE COMPOUNDS
-
The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. Also provided are pharmaceutical compositions containing these compounds and methods of treating a disease or condition mediated by CDK9 using these compounds and compositions.
- -
-
Page/Page column 90
(2012/06/01)
-
- N-ACYL PYRIDINE BIARYL COMPOUNDS AND THEIR USES
-
The present invention provides a compound of general formula:wherein Z2-Z6 include one or two nitrogen atoms as described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.
- -
-
Page/Page column 120
(2012/08/08)
-
- PYRIDINE BIARYL AMINE COMPOUNDS AND THEIR USES
-
The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.
- -
-
Page/Page column 73; 97
(2012/08/08)
-
- N-ACYL PYRIMIDINE BIARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
-
The present invention provides a compound of the general formula (1): wherein one of X and Y is N and the other is an optionally substituted carbon atom, and Z2-Z5 represent one or two nitrogen atoms, as further described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals and as components of pharmaceutical compositions. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds described herein or pharmaceutical compositions comprising such compounds.
- -
-
Page/Page column 161
(2012/08/08)
-
- PYRIMIDINE BIARYL AMINE COMPOUNDS AND THEIR USES
-
The present invention provides a pyrimidine compound of formula (I): wherein one of X and Y but not both is N, and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tantomers, diastereomers, deuterated versions, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds
- -
-
Page/Page column 86-87
(2012/08/08)
-
- HETEROARYL COMPOUNDS AS KINASE INHIBITORS
-
The present invention provides a compound of Formula (I): and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor
- -
-
Page/Page column 65
(2011/04/14)
-
- Heteroaryl Compounds and Their Uses
-
The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. Also provided is a method of treating a disease or condition mediated by CDK9.
- -
-
Page/Page column 24
(2011/02/25)
-
- PYRAZINYLPYRIDINES USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES
-
The present invention provides a compound of Formula (I) and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor.
- -
-
Page/Page column 63-64
(2011/04/14)
-
- Modulation on C- and N-terminal moieties of a series of potent and selective linear tachykinin NK2 receptor antagonists
-
Herein we describe the synthesis of a series of new potent tachykinin NK2 receptor antagonists by the modulation of the Cand N-terminal moieties of ibodutant (MEN 15596, 1). The Nterminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C-terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK2 receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK2 receptor. Selected compounds were tested in vivo confirming their activity as NK2 antagonists. In particular, after both iv and id administration to guinea pig, compound 61b was able to antagonize NK2-induced colonic contractions with a potency and duration-of-action fully comparable to the reference compound 1 (MEN 15596, ibodutant).
- Gensini, Martina,Altamura, Maria,Dimoulas, Tula,Fedi, Valentina,Giannotti, Danilo,Giuliani, Sandro,Guidi, Antonio,Harmat, Nicholas J. S.,Meini, Stefania,Nannicini, Rossano,Pasqui, Franco,Tramontana, Manuela,Triolo, Antonio,Maggi, Carlo Alberto
-
experimental part
p. 65 - 78
(2010/11/16)
-
- 3-AMINO-PYRROLO[3,4-C] PYRAZOLE- 5 (1H, 4H, 6H) CARBALDEHYDE DERIVATIVES AS PKC INHIBITORS
-
The present invention relates to compounds and pharmaceutically acceptable salts of Formulas A and B: (A) and (B) wherein A, B, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications, cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disase pression, virus diseases, inflammatory disorders, or diseases in which the liver is a target organ.
- -
-
Page/Page column 62
(2008/12/08)
-
- 3-AMIDO-PYRROLO[3,4-C]PYRAZOLE-5(1H, 4H,6H) CARBALDEHYDE DERIVATIVES AS INHIBITORS OF PROTEIN KINASE C
-
The present invention relates to compounds and pharmaceutically acceptable salts of Formula (I): wherein X, R1, R2, R3, R4, R5, R6, R7, and R8 are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications (including in particular diabetic retinopathy, nephropathy or neuropathy), cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disease pression, viral diseases, inflammatory disorders, or diseases in which the liver is a target organ
- -
-
Page/Page column 43
(2008/12/08)
-
- Reaction of tetrahydropyranyl azides with 5-R-bicyclo[2.2.1]-2-heptenes
-
The reaction of 5-R-bicyclo[2.2.1]-2-heptenes with 3-azido-4-hydroxy-4-methyltetrahydropyran and 4-azidomethyl-4-hydroxytetrahydropyran, obtained by opening the oxirane ring in epoxytetrahydropyrans with sodium azide, leads to the formation of N-tetrahydropyranylaziridines with 100% stereoselectivity. 1998 Plenum Publishing Corporation.
- Vasil'eva,Abzalov,Safarov
-
p. 778 - 782
(2007/10/03)
-
- SYNTHESIS AND STEREOCHEMISTRY OF 1-OXA-6-HETERASPIROOCTANES. SINGLE-CRYSTAL ANALYSIS OF 6-PHENYL-1-OXA-6-PHOSPHASPIROOCTANE 6-SULFIDE
-
The synthesis of several 1-oxa-6-heteraspirooctanes is reported herein for the first time.Stereochemical analysis via NMR studies and a single crystal X-ray diffraction analysis of 6-phenyl-1-oxa-6-phosphaspirooctane 6-sulfide have been completed and provide the basis for correlations of structures for other members of the families yet unknown.Epoxidation of cis-2,6-diphenyl-4-thianone with dimethyl-oxosulfonium methylide in DMSO led, surprisingly, to a tertiary alcohol, presumably via ring opening of the expected intermediate epoxide.This is the first example of this type of ring opening in the presence of this base but the reaction time was longer than that normally employed in this process.Since the family members of the parent spirooctanes are rare, an X-ray diffraction analysis was performed on 6-phenyl-1-oxa-6-phosphaspirooctane 6-sulfide.This analysis revealed a space group of Pna21 with cell dimensions of: a=13.056(3) Angstroem, b=14.268(3) Angstroem, and c=6.1522(11) Angstroem.The phosphorinane ring assumes a slightly flattened chair conformation with the phenyl-P bond being equatorial and the P=S bond being axial.The plane of the epoxide is virtually coincident with a pseudo-mirror plane through P(6), C(3), C(9) and S(15).The phenyl group is rotated out of this plane by 28.2 deg.Although the P-C distances (ring carbons) are 1.813(3) Angstroem and 1.819(3) Angstroem, respectively, and appear to be about normal, the P-phenyl bond of 1.813(3) Angstroem is longer than in a few model systems.The C(3)-O(1) bond in the epoxide is axial or rather pseudo axial.Ring deformations are consistent with a few model epoxides the structures of which have been identified.
- Satyamurthy, Nagichettiar,Berlin, K. Darrell,Hossain, M. Bilayet,Helm, Dick van der
-
p. 113 - 130
(2007/10/02)
-