- Discovery of thieno[3,2-c]pyridin-4-amines as novel Bruton's tyrosine kinase (BTK) inhibitors
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A novel series of BTK inhibitors bearing thieno[3,2-c]pyridin-4-amine framework as the core scaffold were designed, synthesized and well characterized. In this paper, twenty one compounds displayed variant inhibitory activities against BTK in vitro, and c
- Zhao, Xinge,Xin, Minhang,Wang, Yazhou,Huang, Wei,Jin, Qiu,Tang, Feng,Wu, Gang,Zhao, Yong,Xiang, Hua
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- Convenient amidation of carboxyl group of carboxyphenylboronic acids
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The use of catalysts in the activation of carboxyl groups towards nucleophilic attack and the protection of other functional groups by suitable protecting groups are standard and necessary procedures in amide bond formation. In contrast to the usual metho
- Nowak-Jary, Julia
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- Thieno [3, 2 - c] pyridine compound, its preparation method and application
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The invention relates to a thieno-[3,2-c] pyridine type compound and an application thereof. The compound has a structure shown by a formula (I) in the specification. The compound of which the structure is shown by the formula (I), provided by the invention has a very good effect of inhibiting the activity of Bruton kinase. The invention also relates to the application of the compound in preventing and/or treating diseases which are improved by virtue of BTK (Bruton tyrosine kinase) activity inhibition.
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Paragraph 0237; 0238; 0239; 0250
(2018/09/02)
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- From arylureas to biarylamides to aminoquinazolines: Discovery of a novel, potent TRPV1 antagonist
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Bioisosteric replacement of piperazine with an aryl ring in lead VR1 antagonist 1 led to the biarylamide series. The development of B-ring SAR led to the conformationally constrained analog 70. The resulting aminoquinazoline 70 represents a novel VR1 anta
- Zheng, Xiaozhang,Hodgetts, Kevin J.,Brielmann, Harry,Hutchison, Alan,Burkamp, Frank,Brian Jones,Blurton, Peter,Clarkson, Robert,Chandrasekhar, Jayaraman,Bakthavatchalam, Rajagopal,De Lombaert, Stephane,Crandall, Marci,Cortright, Daniel,Blum, Charles A.
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p. 5217 - 5221
(2007/10/03)
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- Pyrazolopyrimidines as therapeutic agents
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The present invention is directed to pyrazolopyrimidine derivatives of formula (I) wherein the substituents are defined herein, which are useful as kinase inhibitors and as such are useful for affecting angiogenesis and diseases and conditions associated with angiogenesis.
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- PHENYL OR HETEROARYL AMINO ALKANE DERIVATIVES AS IP RECEPTOR ANTAGONIST
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The present invention relates to a phenyl or heteroaryl amino alkane derivatives which are useful as an active ingredient of pharmaceutical preparations. The phenyl or heteroaryl amino alkanes of the present invention have IP receptor antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with IP receptor antagonistic activity. Such diseases include urological diseases or disorder as follows: bladder outlet obstruction, overactive bladder, urinary incontinence, detrusor hyper-reflexia, detrusor instability, reduced bladder capacity, frequency of micturition, urge incontinence, stress incontinence, bladder hyperreactivity, benighn prostatic hypertrophy (BPH), prostatitis, urinary frequency, nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, or idiophatic bladder hypersensitivity. The compounds of the present invention are also useful for treatment of pain including, but not limited to inflammatory pain, neuropathic pain, acute pain, chronic pain, dental pain, premenstrual pain, visceral pain, headaches, and the like; hypotension; hemophilia and hemorrhage; and inflammation, since the diseases also is alleviated by treatment with an IP receptor antagonist.
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- Preparation and uses of conjugated solid supports for boronic acids
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The invention provides novel solid supports comprising dihydroxyalkyl aminoalkyl and dihydroxyalkylaminobenzyl groups, and methods for making and using them. The supports are particularly useful for immobilizing and derivatizing functionalized boronic acids for use in solid phase synthesis, such as those used in combinatorial chemistries. The compositions and methods of the invention are also useful as scavenger solid supports, e.g., in solution-phase parallel synthesis of small molecule libraries, and for use in resin-to-resin transfer reactions via phase transfer of solid supported boronic acids under both aqueous and anhydrous conditions. The methods of the invention provide convergent solid-phase synthesis of symmetrically or unsymmetrically functionalized compounds, such as biphenyl compounds. Also provided are synthesizer devices, e.g., semiautomated parallel synthesizers.
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- Pyrazolopyrimidines as therapeutic agents
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The present invention provides compounds of Formula I, including pharmaceutically acceptable salts and/or prodrugs thereof, where G, R2, and R3 are defined as described herein.
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- Universal solid-phase approach for the immobilization, derivatization, and resin-to-resin transfer reactions of boronic acids
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Boronic acid-containing molecules are employed in a broad range of biological, medicinal, and synthetic applications. These compounds, however, tend to be difficult to handle by solution-phase methods. Herein, this problem is addressed with the development of the first general solid-phase approach for the derivatization of functionalized boronic acids. This approach is based on the use of a diethanolamine resin anchor that facilitates boronic acid immobilization by avoiding the need for exhaustive removal of water in the esterification process. The immobilization of a wide variety of boronic acids onto N,N-diethanolaminomethyl polystyrene (DEAM-PS, 1) can be performed within minutes by simple stirring in anhydrous solvents at room temperature. Evidence for the formation of a bicyclic diethanolamine boronate with putative N-B coordination was shown by 1H NMR analysis of DEAM-PS-supported p-tolylboronic acid. The hydrolytic cleavage of the same model boronic acid from the DEAM-PS resin was studied by UV spectroscopy. Hydrolysis and attachment were shown to occur under a rapidly attained equilibrium, and a large excess of water (> 32 equiv) is required to effect a practically quantitative release of boronic acids from DEAM-PS. Despite their relative sensitivity to water and alcohols, DEAM-PS-bound arylboronic acids functionalized with a formyl, a bromomethyl, a carboxyl, or an amino group can be transformed in good to excellent yields into a wide variety of amines, amides, anilides, and ureas, respectively. Ugi multicomponent reactions on DEAM-PS-supported aminobenzeneboronic acids, derivatization of multifunctional arylboronic acids, and sequential reactions can also be carried out efficiently. These new DEAM-PS-supported arylboronic acids can be employed directly into resin-to-resin transfer reactions (RRTR). This type of multiresin process helps eliminate time-consuming cleavage and transfer operations, thereby considerably simplifying the outlook of combinatorial library synthesis by manual or automated means. This concept was illustrated by a set of optimized procedures for the Suzuki cross-coupling and the borono-Mannich reactions.
- Gravel, Michael,Thompson, Kim A.,Zak, Mark,Berube, Christian,Hall, Dennis G.
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