143924-45-2Relevant articles and documents
CYCLIC AMINOMETHYL PYRIMIDINE DERIVATIVE
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Paragraph 0259-0261, (2016/06/01)
The present invention provides a cyclic aminomethyl pyrimidine derivative and a pharmaceutically acceptable salt thereof with high selectivity for dopamine D4 receptors, which are useful for treating a disease such as attention deficit hyperactivity disorder. Specifically, a compound of formula (1) or a pharmaceutically acceptable salt thereof is provided, wherein n and m are independently 1 or 2; Ra is C1-6 alkyl group, C3-6 cycloalkyl group, or amino group; Rb is hydrogen atom, C1-6 alkyl group or the like, provided that when Ra is amino group, then Rb is hydrogen atom; Rc1 and Rc2 are independently hydrogen atom, or C1-6 alkyl group; Rd1 and Rd2 are independently hydrogen atom, fluorine atom or the like; ring Q is an optionally-substituted pyridyl group or an optionally-substituted isoquinolyl group; and the bond having a dashed line is a single or double bond.
PHARMACEUTICAL CONSISTING OF CYCLIC AMINOMETHYL PYRIMIDINE DERIVATIVE
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Paragraph 0194; 0197; 0198, (2016/10/10)
PROBLEM TO BE SOLVED: To provide a cyclic aminomethyl pyrimidine derivative and a pharmaceutically acceptable salt thereof exhibiting effects on dopamine D4 receptor with high selectivity and useful as a treatment agent of central nervous system diseases such as attention deficit hyperkinesis disorder. SOLUTION: There is provide a compound represented by the formula (1) and a pharmaceutically acceptable salt thereof. (1), where n and m are each independently 1 or 2, Ra is a C1-6 alkyl group, a C3-6 cycloalkyl group or an amino group, Rb is H, a C1-6 alkyl group or an alkyl group-substituted/unsubstituted amino group, Rb is H when Ra is the amino group, Rc1 and Rc2 are each independently H or a C1-6 alkyl group, Rd1 and Rd2 are each independently H, F or a C1-6 alkyl group, a ring Q is substituted/unsubstituted 5- to 10-membered nitrogen-containing heteroaryl group and bond containing break lines is a single bond or a double bond. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
Discovery of 3-methyl-N-(1-oxy-3′,4′,5′,6′- tetrahydro-2′H-[2,4′-bipyridine]-1′-ylmethyl)benzamide (ABT-670), an orally bioavailable dopamine D4 agonist for the treatment of erectile dysfunction
Patel, Meena V.,Kolasa, Teodozyj,Mortell, Kathleen,Matulenko, Mark A.,Hakeem, Ahmed A.,Rohde, Jeffrey J.,Nelson, Sherry L.,Cowart, Marlon D.,Nakane, Masaki,Miller, Loan N.,Uchic, Marie E.,Terranova, Marc A.,El-Kouhen, Odile F.,Donnelly-Roberts, Diana L.,Namovic, Marian T.,Hollingsworth, Peter R.,Chang, Renjie,Martino, Brenda R.,Wetter, Jill M.,Marsh, Kennan C.,Martin, Ruth,Darbyshire, John F.,Gintant, Gary,Hsieh, Gin C.,Moreland, Robert B.,Sullivan, James P.,Brioni, Jorge D.,Stewart, Andrew O.
, p. 7450 - 7465 (2007/10/03)
The goal of this study was to identify a structurally distinct D4-selective agonist with superior oral bioavailability to our first-generation clinical candidate 1a (ABT-724) for the potential treatment of erectile dysfunction. Arylpiperazines such as (heteroarylmethyl)piperazine 1a, benzamide 2, and acetamides such as 3a,b exhibit poor oral bioavailability. Structure-activity relationship (SAR) studies with the arylpiperidine template provided potent partial agonists such as 4d and 5k that demonstrated no improvement in oral bioavailability. Further optimization with the (N-oxy-2-pyridinyl)piperidine template led to the discovery of compound 6b (ABT-670), which exhibited excellent oral bioavailability in rat, dog, and monkey (68%, 85%, and 91%, respectively) with comparable efficacy, safety, and tolerability to 1a. The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein.
TRIAZOLOBENZODIAZEPINES AND THEIR USE AS VASOPRESSIN ANTAGONISTS
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Page/Page column 29, (2010/10/20)
Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein R represents H, C1-6 alkyl, SO2R1, SO2NR1R2, or COR1; R1 and R2 independently represent C1-6alkyl; and Ring A represents a phenyl ring or a pyridinyl ring; may be useful in the treatment of anxiety, cardiovascular disease (including angina, atherosclerosis, hypertension, heart failure, edema, hypernatremia), dysmenorrhoea (primary and secondary), endometriosis, emesis (including motion sickness), intrauterine growth retardation, inflammation (including rheumatoid arthritis), mittlesmerchz, preclampsia, premature ejaculation, premature (preterm) labor and Raynaud's disease.
Preparation of Piperidinylpyridines via Selective Reduction of Bipyridines with Nickel-Aluminum Alloy
Lunn, George
, p. 6317 - 6320 (2007/10/02)
Bipyridines were reduced to piperidinylpyridines in modest yield using nickel-aluminum alloy in potassium hydroxide solution.The reduction was selective, and 3-substituted rings were reduced in preference to 4-substitution.Thus 2,3-bipyridine gave only 2-(3'-piperidinyl)pyridine, 2,4-bipyridine gave only 2-(4'-piperidinyl)pyridine, and 3,4-bipyridine gave only 4-(3'-piperidinyl)pyridine.The symmetrical 2,2'- and 4,4'-bipyridines also gave the corresponding piperidinylpyridines, but the reduction of 3,3'-bipyridine was too sluggish to be practical.The products were identified using 13C NMR spectroscopy, and the 13C NMR spectra of the starting bipyridines were also recorded.
