US 8,198,454 B2 · Amide derivatives and medicinal use thereof

Abstract

The present invention relates to an amide derivative of the formula (1), having a C5a receptor antagonistic action wherein each symbol is as defined in the specification. The above-mentioned amide derivative, an optically active form thereof and a pharmaceutically acceptable salt thereof are promising as an agent for the treatment or prophylaxis of diseases or syndromes caused by inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia reperfusion, trauma, burn, surgical invasion and the like]. Moreover, they are useful as a therapeutic or prophylactic agent for the infectious diseases caused by bacteria and virus that invade via a C5a receptor.

An amide derivative of formula (1)

wherein
R1, R2 and R3 are the same or different and each is selected from the group consisting of a hydrogen atom, an unsubstituted alkyl group, a substituted alkyl group, an unsubstituted alkenyl group, a substituted alkenyl group, an unsubstituted alkynyl group, a substituted alkynyl group, an unsubstituted cycloalkyl group, a substituted cycloalkyl group, an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group, a substituted heteroaryl group, an unsubstituted arylalkyl group, a substituted arylalkyl group, an unsubstituted heteroarylalkyl group, a substituted heteroarylalkyl group, an unsubstituted alkoxy group, a substituted alkoxy group, an aryloxy group, an arylalkyloxy group, an unsubstituted acyloxy group, a substituted acyloxy group, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an acyl group, a mercapto group, an alkylthio group, an alkylsulfonyl group, an amino group, an alkylamino group, a dialkylamino group, a cyclic amino group, an unsubstituted carbamoyl group, a substituted carbamoyl group, an alkoxycarbonyl group, a carboxyl group, an acylamino group, an unsubstituted sulfamoyl group, a substituted sulfamoyl group, and a haloalkyl group, or any two of R1, R2 and R3 in combination with the adjacent carbon atom may form a ring,
a, b, c, d and e are each carbon atom, or 1 or 2 of a, b, c, d and e is(are) nitrogen atom(s), wherein the nitrogen atom may be bonded to an oxygen atom to form an amine oxide, and the rest are carbon atoms,
R4, R5 and R6 are the same or different and each is selected from the group consisting of a hydrogen atom, an unsubstituted alkyl group, a substituted alkyl group, an unsubstituted alkenyl group, a substituted alkenyl group, an unsubstituted alkynyl group, a substituted alkynyl group, an unsubstituted cycloalkyl group, a substituted cycloalkyl group, an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group, a substituted heteroaryl group, an unsubstituted arylalkyl group, a substituted arylalkyl group, an unsubstituted heteroarylalkyl group, a substituted heteroarylalkyl group, an unsubstituted alkoxy group, a substituted alkoxy group, an aryloxy group, an arylalkyloxy group, an unsubstituted acyloxy group, a substituted acyloxy group, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an acyl group, a mercapto group, an alkylthio group, an alkylsulfonyl group, an amino group, an alkylamino group, a dialkylamino group, a cyclic amino group, an unsubstituted carbamoyl group, a substituted carbamoyl group, an alkoxycarbonyl group, a carboxyl group, an acylamino group, an unsubstituted sulfamoyl group, a substituted sulfamoyl group, a haloalkyl group, and a haloalkyloxy group,
A is selected from the group consisting of an unsubstituted cycloalkyl group, a substituted cycloalkyl group, an unsubstituted aryl group, a substituted aryl group, an unsubtituted heteroaryl group, and a substituted heteroaryl group,
W1 and W2 are the same or different and each is a bond, an unsubstituted alkylene(Cn), or a substituted alkylene(Cn) wherein n is an integer of 1 to 3,
X is oxygen atom or sulfur atom,
Y is selected from the group consisting of a bond, an oxygen atom, —CO—, —N(R7)— wherein R7 is a hydrogen atom, an unsubstituted alkyl group or a substituted alkyl group, —SOm— wherein m is an integer of 0 to 2, —CON(R8)— wherein R8 is a hydrogen atom, an unsubstituted alkyl group or a substituted alkyl group, and —N(R9)CO— wherein R9 is a hydrogen atom, an unsubstituted alkyl group or a substituted alkyl group, and
Z is an unsubstituted alkylene group or a substituted alkylene group,
an optically active form thereof or a pharmaceutically acceptable salt thereof.

7 more elements

Facts

Application

12/458,095Filed 30 Jun 2009 · continuation

Priority

JP 2000-28054014 Sep 2000

Published

US 2010/0041656 A118 Feb 2010

Granted

12 Jun 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification61 codes

C07D 213/40
Radicals substituted by singly-bound nitrogen atoms: acylated substituent nitrogen atom
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 11/00
Drugs for disorders of the respiratory system

Family

PCT/JP01/07977Parent of this continuation · filed 14 Sep 2001

US 2010/0041656 A1Pre-grant publication · published 18 Feb 2010

Application10/380,502Parent of this continuation

US 7,855,297 B2Parent of this continuation

US 2004/0138223 A1Published application

US 8,198,454 B2This patent

From the US filing history. Foreign family members aren’t listed.

Amide derivatives and medicinal use thereof

Life of this patent

Amide derivatives and medicinal use thereof

Life of this patent

Abstract

Claims37