- BROMODOMAIN INHIBITORS AND USES THEREOF
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The present invention relates to compounds of formula (I): [INSERT FORMULA (1)] and to salts thereof, wherein R1, R2, Rc, and Rd have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.
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- Synthesis and SAR of Imidazo[1,5-a[pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease
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Alzheimer's disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine4 receptor (5-HT4R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo[1,5-a] pyridine derivatives as 5-HT4R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound 5a as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition.
- Nirogi, Ramakrishna,Mohammed, Abdul Rasheed,Shinde, Anil K.,Bogaraju, Narsimha,Gagginapalli, Shankar Reddy,Ravella, Srinivasa Rao,Kota, Laxman,Bhyrapuneni, Gopinadh,Muddana, Nageswara Rao,Benade, Vijay,Palacharla, Raghava Chowdary,Jayarajan, Pradeep,Subramanian, Ramkumar,Goyal, Vinod Kumar
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p. 289 - 301
(2015/09/21)
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- 2′ Biaryl amides as novel and subtype selective M1 agonists. Part I: Identification, synthesis, and initial SAR
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Biaryl amides were discovered as novel and subtype selective M1 muscarinic acetylcholine receptor agonists. The identification, synthesis, and initial structure-activity relationships that led to compounds 3j and 4c, possessing good M1 agonist potency and intrinsic activity, and subtype selectivity for M1 over M2-5, are described.
- Budzik, Brian,Garzya, Vincenzo,Shi, Dongchuan,Foley, James J.,Rivero, Ralph A.,Langmead, Christopher J.,Watson, Jeannette,Wu, Zining,Forbes, Ian T.,Jin, Jian
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scheme or table
p. 3540 - 3544
(2010/08/22)
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- Non-aromatic A-ring replacement in the triaryl bis-sulfone CB2 receptor inhibitors
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The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inh
- Gilbert, Eric J.,Zhou, Guowei,Wong, Michael K.C.,Tong, Ling,Shankar, Bandarpalle B.,Huang, Chunli,Kelly, Joseph,Lavey, Brian J.,McCombie, Stuart W.,Chen, Lei,Rizvi, Razia,Dong, Youhao,Shu, Youheng,Kozlowski, Joseph A.,Shih, Neng-Yang,Hipkin, R. William,Gonsiorek, Waldemar,Malikzay, Asra,Lunn, Charles A.,Favreau, Len,Lundell, Daniel J.
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scheme or table
p. 608 - 611
(2010/05/02)
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- CANNABINOID RECEPTOR LIGANDS
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There are disclosed compounds of the formula I: or a pharmaceutically acceptable salt of the compound, which exhibit anti-inflammatory and immunomodulatory activity. Also disclosed are pharmaceutical compositions containing said compounds.
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Page/Page column 51
(2010/02/05)
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- N-acyl cyclic amine derivatives
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The invention relates to compounds represented by the general formula [I][wherein Ar means an aryl group or a heteroaryl group which may have a substitutive group selected from a group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group; R1 means a C3-C6 cycloalkyl group which is substitutable with a fluorine atom; R2 and R4 mean hydrogen atoms, groups represented by -(A1)m-NH-B or the like; R3 and R5 mean hydrogen atoms, C1-C6 aliphatic hydrocarbon groups or the like which are substitutable with a lower alkyl group(s); n means 0 or 1; and X means an oxygen atom or a sulfur atom]. Compounds according to the invention, since they not only have potent selective antagonistic activity against muscarinic M3 receptors but also exhibit excellent oral activity, durability of action and pharmacokinetics, are very useful as safe and effective remedies against respiratory, urinary and digestive diseases with little adverse side effects.
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