22246-81-7Relevant academic research and scientific papers
Fused bicyclic Gly-Asp β-turn mimics with specific affinity for GPIIb- IIIa
Fisher, Matthew J.,Arfstan, Ann E.,Giese, Ulrich,Gunn, Bruce P.,Harms, Cathy S.,Khau, Vien,Kinnick, Michael D.,Lindstrom, Terry D.,Martinelli, Michael J.,Mest, Hans-Jürgen,Mohr, Michael,Morin Jr., John M.,Mullaney, Jeffrey T.,Nunes, Anne,Paal, Michael,Rapp, Achim,Rühter, Gerd,Ruterbories, Ken J.,Sall, Daniel J.,Scarborough, Robert M.,Schotten, Theo,Sommer, Birgit,Stenzel, Wolfgang,Towner, Richard D.,Um, Suzane L.,Utterback, Barbara G.,Vasileff, Robert T.,V?elkers, Silke,Wyss, Virginia L.,Jakubowski, Joseph A.
, p. 4875 - 4889 (1999)
Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure activity studies centered on the bicyclic β-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6,5-bicyclic, and 6,7-bicyclic structures provide compounds with affinity for GPIIb-IIIa. Within the 6,6-series, isoquinoline, tetralin, tetralone, and benzopyran nuclei yield potent antagonists that are specific for GPIIb-IIIa. Attachment of the arginine isostere (benzamidine) to the supporting nucleus can be accomplished with an ether or amide linkage, although the latter enhances activity. Several compounds in this series provided measurable blood levels after oral dosing. Conversion of the acid moiety in these molecules to an ester generally provided compounds which gave greater systemic exposure after oral administration. Absolute bioavailabilities in the rat for the ethyl ester prodrug derivatives of the tetralin, tetralone, and benzopyran analogues of 3 were 28%, 23%, and 24%, respectively.
1-[2-(1-Cyclobutylpiperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]propan-1-one: a Histamine H3 Receptor Inverse Agonist with Efficacy in Animal Models of Cognition
Shinde, Anil Karbhari,Badange, Rajesh Kumar,Reballi, Veena,Achanta, Pramod Kumar,Bojja, Kumar,Manchineella, Sravanthi,Rao Muddana, Nageswara,Subramanian, Ramkumar,Choudary Palacharla, Raghava,Benade, Vijay,Jayarajan, Pradeep,Thentu, Jagadeesh Babu,Lingavarapu, Bujji Babu,Yarra, Sivasekhar,Kagita, Narendra,Rao Doguparthi, Mallikarjuna,Mohammed, Abdul Rasheed,Nirogi, Ramakrishna
, (2021/11/23)
A series of chemical optimizations, which was guided by in vitro affinity at histamine H3 receptor (H3R), modulation of lipophilicity, ADME properties and preclinical efficacy resulted in the identification of 1-[2-(1-cyclobutylpiperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]propan-1-one (45 e) as a potent and selective (Ki=4.0 nM) H3R inverse agonist. Dipsogenia induced by (R)-α-methylhistamine was dose dependently antagonized by 45 e, confirming its functional antagonism at H3R. It is devoid of hERG and phospholipidosis issues. Compound 45 e has adequate oral exposures and favorable half-life in both rats and dogs. It has demonstrated high receptor occupancy (ED80=0.22 mg/kg) and robust efficacy in object recognition task and, dose dependently increased acetylcholine levels in brain. The sub-therapeutic doses of 45 e in combination with donepezil significantly increased acetylcholine levels. The potent affinity, selectivity, in vivo efficacy and drug like properties together with safety, warrant for further development of this molecule for potential treatment of cognitive disorders associated with Alzheimer's disease.
Synthesis of novel benzotriazoloazepine derivatives
Zhang, Wei,Han, Rong-Bi,Zhang, Wen-Bin,Jiang, Ri-Shan,Piao, Feng-Yu
, p. 29 - 32 (2013/04/10)
Eight new benzotriazoloazepine derivatives have been synthesized starting from 7-methoxy-2,3,4,5-tetrahydro-1H-2-benzo[c]azepin-1-one. The compounds 2a-c have been synthesized by the reaction of 7-methoxy-2,3,4,5-tetrahydro-1H-2- benzo[c]azepin-1-thione w
SUBSTITUTED AZEPINES AS HISTAMINE H3 RECEPTOR ANTAGONISTS, PREPARATION AND THERAPEUTIC USES
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Page 32, (2010/11/30)
The present invention discloses novel substituted azepine compounds of Formula (I) or pharmaceutically acceptable salts thereof which have selective histamine-H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such azepines as well as methods of using them to treat obesity and other histamine H3 receptor-related diseases.
2-CYANOPYRROLOPYRIMIDINES AND PHARMACEUTICAL USES THEREOF
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Page/Page column 31, (2010/02/08)
The invention relates to pyrrolo pyrimidines of formula (I), wherein Y represents -(CH2)t-O- or -(CH2)r-S-, p is 1 or 2, r is 1, 2 or 3, t is 1, 2 or 3, or Y is -(CH2)j- or -CH=CH-, j is 1 or 2; p is 1 or 2, or Y is -(CH2)f-, f is 1 or 2, p is 1, and the further radicals and symbols have the meaning as defined herein; their preparation, their use as pharmaceuticals, pharmaceutical compositions containing them, the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment of neuropathic pain and to a method for the treatment of such a disease in animals, especially in humans.
Benzene-fused heterocycle derivatives and drugs containing the same as the active ingredient
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, (2008/06/13)
A benzene-fused heteroring derivative of formula (I) 1, wherein all symbols are the same as described in the specification, and a non-toxic salt thereof. The compound of formula (I) has an inhibitory activity against cysteine protease and therefore it is
