- 3-Substituted Quinolines as RORγt Inverse Agonists
-
We have previously reported the syntheses of a series of 3,6-disubstituted quinolines as modulators of the retinoic acid receptor-related orphan receptor gamma t (RORγt). These molecules are potent binders but are high molecular weight and they exhibited poor solubility at pH 2 and pH 7. This manuscript details our efforts at improving physical chemical properties for this series of compounds by increasing the diversity at the 3-position (i.e. introducing heteroatoms and lowering the molecular weight). These efforts have led to molecules which are potent binders with improved solubility.
- Tanis, Virginia M.,Venkatesan, Hariharan,Cummings, Maxwell D.,Albers, Michael,Kent Barbay,Herman, Krystal,Kummer, David A.,Milligan, Cynthia,Nelen, Marina I.,Nishimura, Rachel,Schlueter, Thomas,Scott, Brian,Spurlino, John,Wolin, Ronald,Woods, Craig,Xue, Xiaohua,Edwards, James P.,Fourie, Anne M.,Leonard, Kristi
-
-
Read Online
- Cross-Electrophile Coupling of Unactivated Alkyl Chlorides
-
Alkyl chlorides are bench-stable chemical feedstocks that remain among the most underutilized electrophile classes in transition metal catalysis. Overcoming intrinsic limitations of C(sp3)-Cl bond activation, we report the development of a novel organosilane reagent that can participate in chlorine atom abstraction under mild photocatalytic conditions. In particular, we describe the application of this mechanism to a dual nickel/photoredox catalytic protocol that enables the first cross-electrophile coupling of unactivated alkyl chlorides and aryl chlorides. Employing these low-toxicity, abundant, and commercially available organochloride building blocks, this methodology allows access to a broad array of highly functionalized C(sp2)-C(sp3) coupled adducts, including numerous drug analogues.
- Sakai, Holt A.,Liu, Wei,Le, Chi,MacMillan, David W. C.
-
-
Read Online
- Nickel-Catalyzed Addition of C–C Bonds of Amides to Strained Alkenes: The 1,2-Carboaminocarbonylation Reaction
-
C(aryl)–C(═O) bonds of aryl amides can be activated and added across alkenes with the aid of a nickel catalyst. This 1,2-carboaminocarbonylation reaction enables the dicarbofunctionalization of alkenes with an atom economy of 100%.
- Ito, Yuri,Kodama, Takuya,Nakatani, Syun,Shiraki, Ryota,Tobisu, Mamoru
-
supporting information
p. 662 - 666
(2022/02/05)
-
- Biocatalytic Strategy for the Highly Stereoselective Synthesis of CHF2-Containing Trisubstituted Cyclopropanes
-
The difluoromethyl (CHF2) group has attracted significant attention in drug discovery and development efforts, owing to its ability to serve as fluorinated bioisostere of methyl, hydroxyl, and thiol groups. Herein, we report an efficient biocat
- Carminati, Daniela M.,Decaens, Jonathan,Couve-Bonnaire, Samuel,Jubault, Philippe,Fasan, Rudi
-
supporting information
p. 7072 - 7076
(2021/02/27)
-
- Novel Inhibitors of an Insect Pest Chitinase: Design and Optimization of 9-O-Aromatic and Heterocyclic Esters of Berberine
-
OfChi-h, a lepidopteran-exclusive glycoside hydrolase family 18 (GH18) chitinase from the agricultural insect pest Ostrinia furnacalis, is a promising molecular target candidate for pest control and management. Berberine (BER), a traditional Chinese medic
- Chen, Lei,Cheng, Jiagao,Qian, Xuhong,Shao, Xusheng,Yang, Qing,Zhu, Ling
-
p. 7526 - 7533
(2021/07/26)
-
- NOVEL NUCLEOSIDE OR NUCLEOTIDE DERIVATIVES, AND USES THEREOF
-
The present disclosure relates to a novel nucleoside or nucleotide derivative, a racemate thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition for preventing or treating viral infection-associated diseases, containing the same as an active ingredient.
- -
-
Paragraph 0063; 0090
(2020/12/10)
-
- PROLONGED ECTOPARASITE-CONTROLLING AGENT FOR ANIMAL
-
A compound represented by Formula (1) can be used as a prolonged ectoparasite-controlling agent for an animal. A preparation for systemic application for use in prolonged control of an ectoparasite in an animal include the compound. A method for prolonged
- -
-
Paragraph 0161; 0168
(2019/04/16)
-
- HETEROARYL COMPOUNDS AS KINASE INHIBITOR
-
Provided herein are heteroaryl compounds of formula (I) having activity on a receptor protein tyrosine kinase, wherein R 1, R 2, R 3, A, Q, Z, X and W are set forth in the description, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 77-78
(2019/10/04)
-
- HETEROARYL LINKED QUINOLINYL MODULATORS OF RORγT
-
The present invention comprises compounds of Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification, The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndro
- -
-
Paragraph 0189-0192
(2016/11/21)
-
- PHENYL LINKED QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also
- -
-
Paragraph 0195
(2015/04/21)
-
- HETEROARYL LINKED QUINOLINYL MODULATORS OF ROR?T
-
The present invention comprises compounds of Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification, The invention also
- -
-
Page/Page column 41; 42
(2015/05/05)
-
- HETEROARYL LINKED QUINOLINYL MODULATORS OF RORgammat
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7 R8, and R9 are defined in the specification. The invention also
- -
-
Paragraph 0191; 0192
(2015/04/21)
-
- METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0188; 0189
(2015/04/21)
-
- METHYLENE LINKED QUINOLINYL MODULATORS OF ROR-GAMMA-T
-
The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Page/Page column 59; 60
(2015/05/05)
-
- PHENYL LINKED QUINOLINYL MODULATORS OF ROR-GAMMA-T
-
The present invention comprises compounds of Formula I. Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The inve
- -
-
Page/Page column 50
(2015/05/05)
-
- QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0361; 0362
(2015/04/28)
-
- Nematicidal activities of diamides with diphenylacetylene scaffold against Meloidogyne Incognita
-
With the goal of searching for new potential nematicides with high activity and low toxicity, new molecules are needed as potential prototypes for the synthesis of new nematicidal compounds. A series of novel diamides based on diphenylacetylene scaffold were designed and synthesised. The conformation of the amide was restricted through the ten-membered H-bonded ring. Their structures were characterised by 1H NMR, 13C NMR, 19F NMR, and high-resolution mass spectrometry. The preliminary bioassays evaluated against Meloidogyne Incognita indicated that most of the title compounds were endowed with moderate-to-good activities at the concentration of 25mgL-1. In particular, compounds 9a, 9c, 9g, 9h, 9k, and 9l displayed >50% nematicidal activity at 5mgL-1. It is possible that the novel diamides with diphenylacetylene scaffold, which possess good nematicidal activities, provide distinct nematicidal chemotypes that can be used as leads for further optimisation.
- Li, Jiling,Zhang, Zhicheng,Xu, Xiaoyong,Shao, Xusheng,Li, Zhong
-
p. 1543 - 1549
(2015/10/20)
-
- METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0541; 0542
(2014/05/07)
-
- HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0298; 0299
(2014/05/07)
-
- HETEROARYL LINKED QUINOLINYL MODULATORS OF RORGAMMAT
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndr
- -
-
Page/Page column
(2019/06/13)
-
- Design, synthesis and insecticidal activity of novel anthranilic diamides with benzyl sulfide scaffold
-
A series of novel anthranilic diamides with benzyl sulfide scaffold were synthesized, in which N-pyridylpyrazole moiety generally regarded as key pharmacophore was abandoned. The target compounds were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The preliminary bioassays indicated that half of the title compounds were endowed with good insecticidal activities against armyworm (Mythimna sepatara) at the concentration of 500 mg/L. Exhilaratingly, the synthesized compound 3a was also active against Tetranychus cinnabarinus at 100 mg/L. The difference in activities between the target compounds was influenced by the substituents, which provided some hints for further investigation on structure modifications.
- Chen, Yin-Bo,Li, Ji-Ling,Shao, Xu-Sheng,Xu, Xiao-Yong,Li, Zhong
-
p. 673 - 676
(2013/07/26)
-
- Complementary regioselectivity in Rh(III)-catalyzed insertions of potassium vinyltrifluoroborate via C-H activation: Preparation and use of 4-trifluoroboratotetrahydroisoquinolones
-
Potassium vinyltrifluoroborate was found to be an efficient partner with benzamide derivatives for Rh(III)-catalyzed annulations. 4- Trifluoroboratotetrahydroisoquinolones were generated under mild conditions, affording a regioisomerically complementary substitution pattern to other alkenes in related reactions. These new boron-containing building blocks were derivatized by N-arylations, retaining the boron substituent for further elaboration.
- Presset, Marc,Oehlrich, Daniel,Rombouts, Frederik,Molander, Gary A.
-
supporting information
p. 1528 - 1531
(2013/06/27)
-
- INDOLES AS MODULATORS OF NICOTINIC ACETYLCHOLIN RECEPTOR SUBTYPE ALPHA-71
-
This invention relates to modulation of the α7 nicotinic acetylcholine receptor (nAChR) by a compound of formula (I) or a salt thereof: Formula (I)
- -
-
Page/Page column 38
(2009/12/02)
-
- PIPERIDINE DERIVATIVES AND METHODS OF USE THEREOF
-
The present invention relates to Compounds of Formula (I), compositions comprising the compounds, and methods of using the compounds to treat or prevent pain, diabetes, a diabetic complication, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) in a patient.
- -
-
Page/Page column 57-58
(2008/12/08)
-
- (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6- (trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (YM580) as an orally potent and peripherally selective nonsteroidal androgen receptor antagonist
-
A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that compound 33 was a potent AR antagonist, and subsequent optical resolution provided (+)-(2R,5S)4-[4-cyano-3-(trifluoromethyl)phenyl]-2, 5-dimethyl-N-[6(triflouromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound 33a decreased the weight of rat ventral prostate in a dose-dependent manner (ED50 = 2.2 mg/kg/day), and induced the maximum antiandrogenic effect, comparable to that of surgical castration, without significantly affecting serum testosterone levels. Compound 33a is a promising clinical candidate for prostate cancer monotherapy.
- Kinoyama, Isao,Taniguchi, Nobuaki,Toyoshima, Akira,Nozawa, Eisuke,Kamikubo, Takashi,Imamura, Masakazu,Matsuhisa, Akira,Samizu, Kiyohiro,Kawanimani, Eiji,Niimi, Tatsuya,Hamada, Noritaka,Koutoku, Hiroshi,Furutani, Takashi,Kudoh, Masafumi,Okada, Minoru,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
-
p. 716 - 726
(2007/10/03)
-
- NOVEL PHENYLAMINOPYRIMIDINE DERIVATIVES AS INHIBITORS OF BCR-ABL KINASE
-
The present invention relates to novel intermediates useful for the preparation of novel phenylaminopyrimidine derivatives, novel phenylaminopyrimidine derivatives. Pharmaceutical composition containing the novel phenylaminopyrimidine derivatives and processes for their preparation. The invention particularly relates to novel Phenyl pyrimidine amine derivatives of the general formula (I). The novel compounds of the formula 1 can be used in the therapy of Chronic Myeloid Leukemia (CML). Since the IC50; 191 values of these molecules are in the range 0.1 to 10.0 nm, these novel compounds are potentially useful for the treatment of CML.
- -
-
Page/Page column 36-37
(2008/06/13)
-
- ARYL-SUBSTITUTED PIPERAZINE DERIVATIVES
-
Aryl-substituted piperazine derivatives are provided. Such compounds may be used to modulate MCH receptor activity in vivo or in vitro, and are particularly useful in the treatment of a variety of metabolic, feeding and sexual disorders in humans, domesti
- -
-
Page/Page column 36
(2010/02/15)
-
- SUBSTITUTED 1-BENZYL-4-SUBSTITUTED PIPERAZINE ANALOGUES
-
Compounds of Formula I are provided, in which variables are as described herein: Such compounds may be used to modulate MCH binding to MCH receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of metabolic, feeding and s
- -
-
Page/Page column 44
(2008/06/13)
-
