- SUBSTITUTED THIAZOLE DERIVATIVES BEARING 3-PYRIDYL GROUPS, PROCESS FOR PREPARING THE SAME AND USE THEREOF
-
The present invention provides a pharmaceutical composition having a steroid C17,20-lyase inhibitory activity, which is useful as a prophylactic or therapeutic agent of prostatism, tumor such as breast cancer and the like, more particularly, a steroid C17,20-lyase inhibitor containing a compound represented by the formula: wherein A1 is an aromatic hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, one of A2 and A3 is a hydrogen atom, a halogen atom, a C1-4 aliphatic hydrocarbon group optionally having substituents or an optionally esterified carboxyl group, the other of A2 and A3 is an aromatic hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, and at least one of A1, A2 and A3 is a 3-pyridyl group optionally having substituents, or a salt thereof or a prodrug thereof.
- -
-
Page/Page column 37
(2008/06/13)
-
- Protoberberines from Reissert-Compounds, IV. A Novel Synthesis of (+/-)-Alamaridine and (+/-)-epi-Alamaridine
-
A novel synthesis of 8-methylisoquinonaphthyridinium salts 7 is reported using the intramolecular cyclization of the 1-substituted isoquinolines 5 as the key step, which in turn are obtained by alkylation of the Reissert compound 1.The salts 7 can be reduced by NaBH4 yielding the 8α- and 8β-methylstereomers (+/-)-alamaridine and (+/-)-epi-alamaridine 9c and 11c, respectively. - Keywords.Reissert compounds; Intramolecular cyclization; 8-Methylisoquinonaphthyridinium chlorides; (+/-)-Alamaridine; (+/-)-epi-Alamaridine.
- Reimann, E.,Renz, H.
-
p. 1397 - 1406
(2007/10/02)
-
- Antiulcer Agents. 2. Gastric Antisecretory, Cytoprotective, and Metabolic Properties of Substituted Imidazolpyridines and Analogues
-
The search for a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazopyridine, Sch 28080 (27), a compound that exhibits gastric antisecretory and cytoprotective properties and has undergone clinical evaluation as an antiulcer agent, has culminated in the identification of four related compounds that exhibit pharmacologic profiles similar to that of 27.In three of these potential successors an amino group functions as a surrogate for the 3-cyanomethyl substituent of the prototype.The present work concerns, in addition to an evaluation of the structure-activity relationships of a series of analogues of 27, preliminary studies of the pharmacodynamics and metabolism of 27, performed with the aid of cyano carbon labeled versions of the drug (13C labeled; 28; 14C labeled, 29).These studies have shown that 27 is well-absorbed and extensively metabolized and that the major metabolite of 27 is the thiocyanate anion.A similar study performed on 3-amino-2-methyl-8-(phenylmethoxy)imidazopyridine, labeled at the 3-position with carbon-13 (41) or carbon-14 (42), revealed that this compound, which has an antisecretory/cytoprotective profile comparable to that of 27, is also metabolized to thiocyanate anion, although this must occur via a different mechanism.The chemistry section includes a discussion of the potential sites of protonation of the pharmacologically similar 3-amino analogue 40 and the structurally related imidazopyrazine 67.Predictions based on charge density and protonation product stabilities are presented.That N1 is the site of protonation in these analogues has been definitively demonstrated by X-ray crystal structure analysis, which alsounequivocally established the assigned imidazopyrazine ring structure.
- Kaminski, James J.,Hilbert, James M.,Pramanik, B. N.,Solomon, Daniel M.,Conn, David J.,et al.
-
p. 2031 - 2046
(2007/10/02)
-
- REACTION OF 1-ETHOXY-1-BUTEN-3-ONE WITH AMINES
-
In the reaction of 1-ethoxy-1-buten-3-one with ammonia and primary and secondary amines the alkoxy group is substituted by an amino group.In the reaction with ammonia 1-amino-1-buten-3-one condenses with the formation of 2-methyl-5-acetylpyridine.
- Markova, N. K.,Zaichenko, Yu. A.,Tsil'ko, A. E.,Maretina, I. A.
-
p. 876 - 880
(2007/10/02)
-
