DERIVADOS DE DIAZABICICLOALCANO CON ACTIVIDAD ANTAGONISTA DE NK1

• Main Authors: IWEMA BAKKER, WOUTER I, KUIL, GIJSBERT D, HESSELINK, MAYKE B, DE BOER, DIRK, VAN MAARSEVEEN, JAN H, VAN SCHARRENBURG, GUUSTAAF J. M, MCCREARY, ANDREW C, COOLEN, HEIN K. A. C
• Format: Patent
• Language: Spanish
• Published: 09.02.2005
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Un grupo de singulares derivados de diazabicicloalcano que tienen interesante actividad antagonista del receptor NK1 de neuroquinina, representados por la fórmula general (1) en donde: R1 representa fenilo, 2-indolilo, 3-indolilo, 3-indazolilo o benzo[b]tiofen-3-ilo, cuyos grupos pueden estar sustituidos con halógeno o alquilo C1-3; R2 y R3 representan independientemente halógeno, H, OCH3, CH3 y CF3, R4, R5 y R6 independientemente representan H, OH, O-alquilo C1-4, CH2OH, NH2, dialquil (C1-3)N, pirrolidin-1-ilo, piperidin-1-ilo, morfolin-4-ilo o morfolin-4-ilo sustituido con uno o dos grupos metilo o metoximetilo, morfolin-4-ilamino, morfolin-4-ilmetilo, imidazol-1-ilo, tiomorfolin-4-ilo, 1,1-dioxotiomorfolin-4-ilo o 3-oxa-8-azabiciclo[3.2.1]oct-8-ilo; R4 y R5 juntos pueden representar un grupo ceto, un grupo 1,3-dioxan-2-ilo o un grupo 1,3-dioxolan-2-ilo, X representa O ó S; n tiene el valor de 1, 2 o 3; a es el átomo de C asimétrico 8a, 9a o 10a cuando n es igual a 1, 2 o 3 respectivamente. También se refiere a un método para la preparación de los compuestos, y a composiciones farmacéuticas que contienen al menos uno de estos compuestos como un ingrediente activo. The present invention relates to a group of unique diazabicyclo alkane derivatives having interesting neurokinin-NK1 receptor antagonistic activity represented by the general formula (1) wherein: R1 represents phenyl, 2-indolyl, 3-indolyl, 3-indazolyl or benzo[b]thiophen-3-yl, which groups may be substituted with halogen or alkyl (1-3C), R2 and R3 independently represent halogen, H, OCH3, CH3 and CF3, R4, R5 and R6 independently represent H, OH, O-alkyl(1-4C), CH2OH, NH2, dialkyl(1-3C)N, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or morpholin-4-yl substituted with one or two methyl or methoxymethyl groups, morpholin-4-ylamino, morpholin-4-ylmethyl, imidazol-1-yl, thiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl or 3-oxa-8-azabicyclo[3.2.1]oct-8-yl; R4 and R5 together may represent a keto, a 1,3-dioxan-2-yl or a 1,3-dioxolan-2-yl group, X represents either O or S, n has the value of 1, 2 or 3, a is the asymmetrical carbon atom 8a, 9a or 10a when n equals 1, 2 or 3 respectively The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions containing at least one of these compounds as an active ingredient.