US 2010/0144698 A1Published application

Substituted azetidinones

AssigneeDaiamed

InventorsThomas Bannister, Cassandra Celatka, Nizal S. Chandrakumar, Hongfeng Deng, Zihong Guo, Lei Jin, Tsveltelina Lazarova, Jian Lin, Scott T. Moe, Pamela Nagafuji, Manuel Navia, Amy Ripka, Michael J. Rynkiewicz, Kerry L. Spear, James E. Stickler, Roger Xie

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Abstract

Compounds are provided which have the structure Wherein A, B, C, D, m, Y, Ra, Rc, Rd, and Rd′ are as described herein, and which are useful as inhibitors of tryptase, thrombin, trypsin, Factor Xa, Factor VIIa, Factor XIa, and urokinase-type plasminogen activator and may be employed in preventing and/or treating asthma, chronic asthma, allergic rhinitis, and thrombotic disorders.

Claims20

Dependent claims

A compound according to the following structure or a pharmaceutically acceptable salt thereof:

wherein
A, B, C, D and m are defined such that
comprises a structure selected from:
wherein
Rz1 is a member independently selected from H and CH3
Rz2 is a member selected from H and C1-C4 alkyl
Rz3 is a member selected from H and NH2
X1 is a member selected from C and N
k1 is an integer selected from 0 and 1;
X is a member selected from S and O;
Y is a member selected from a bond, C═O, and SO2;
Ra is a member selected from NR7R8, substituted or unsubstituted heteroaryl, and
wherein
R7 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
R8 is a member selected from substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
and
k2 is an integer selected from 1, 2 and 3;
Rc is a member selected from H and substituted or unsubstituted C1-C5 alkyl;
Rd is a member selected from R16 and CH2R16
wherein
R16 is a member selected from C(O)R18,
wherein
R18 is a member selected from OR21, NR19N20, and NR19SO2R20
Rz4 is a member selected from C1-C5 alkyl, C3-C6 cycloalkyl, and substituted or unsubstituted phenyl
Rz5 is a member selected from H, C1-C5 alkyl, C3-C6 cycloalkyl, and substituted or unsubstituted phenyl
Rz6 is a member selected from C1-C5 alkyl and C3-C6 cycloalkyl
wherein
R21 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted aryl;
R19 is a member selected from H and substituted or unsubstituted C1-C5 alkyl;
and
R20 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
and
R19 and R20 can be optionally joined, together with the atoms to which they are attached, to form a 5 or 6 membered ring;
and
Rd′ is a member selected from H, substituted or unsubstituted C1-C5 alkyl, and substituted or unsubstituted C3-C6 cycloalkyl.

32 more elements

A compound according to the following structure or a pharmaceutically acceptable salt thereof:

wherein
A is a member selected from CH2, O and S
B is a member independently selected from unsubstituted alkyl, —S—, and —O—;
m is an integer selected from 0, 1 and 2;
C is a member selected from a bond and —O—;
D is a member selected from
X is a member selected from S and O;
Y is a member selected from a bond and C═O;
Ra is
wherein k2 is an integer selected from 1, 2 and 3;
Rc is a member selected from H and substituted or unsubstituted C1-C5 alkyl;
Rd is a member selected from R16 and CH2R16
wherein
R16 is a member selected from C(O)R18,
wherein
R18 is a member selected from OR21, NR19N20, and NR19SO2R20
Rz4 is a member selected from C1-C5 alkyl, C3-C6 cycloalkyl, and substituted or unsubstituted phenyl
Rz5 is a member selected from H, C1-C5 alkyl, C3-C6 cycloalkyl, and substituted or unsubstituted phenyl
Rz6 is a member selected from C1-C5 alkyl and C3-C6 cycloalkyl
wherein
R21 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted aryl;
R19 is a member selected from H and substituted or unsubstituted C1-C5 alkyl;
and
R20 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
and
R19 and R20 can be optionally joined, together with the atoms to which they are attached, to form a 5 or 6 membered ring;
and
Rd′ is a member selected from H, substituted or unsubstituted C1-C5 alkyl, and substituted or unsubstituted C3-C6 cycloalkyl.

25 more elements

A compound according to the following structure or a pharmaceutically acceptable salt thereof:

wherein
A is a member selected from CH2, O and S B is a member independently selected from unsubstituted alkyl, —S—, and —O—;
m is an integer selected from 0, 1 and 2;
C is a member selected from a bond and —O—;
D is a member selected from
X is a member selected from S and O;
Y is a member selected from a bond, C═O, and SO2;
Ra is a member selected from NR7R8 and substituted or unsubstituted heteroaryl
wherein
R7 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
and
R8 is a member selected from substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
Rc is a member selected from H and substituted or unsubstituted C1-C5 alkyl;
Rd is a member selected from R16 and CH2R16
wherein
R16 is a member selected from C(O)R18,
wherein
R18 is NR19R20
Rz4 is a member selected from C1-C5 alkyl, C3-C6 cycloalkyl, and substituted or unsubstituted phenyl
Rz5 is a member selected from H, C1-C5 alkyl, C3-C6 cycloalkyl, and substituted or unsubstituted phenyl
Rz6 is a member selected from C1-C5 alkyl and C3-C6 cycloalkyl
wherein
R19 is a member selected from substituted or unsubstituted C1-C5 alkyl;
and
R20 is a member selected from substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
and
R19 and R20 are joined, together with the atoms to which they are attached, to form a 5 membered ring;
and
Rd′ is a member selected from H, substituted or unsubstituted C1-C5 alkyl, and substituted or unsubstituted C3-C6 cycloalkyl.

26 more elements

A compound according to the following structure or a pharmaceutically acceptable salt thereof:

wherein
A is a member selected from CH2, O and S
B is a member independently selected from unsubstituted alkyl, —S—, and —O—;
m is an integer selected from 0, 1 and 2;
C is a member selected from a bond and —O—;
D is a member selected from
X is a member selected from S and O;
Y is a member selected from a bond, C═O, and SO2;
Ra is a member selected from NR7R8 and substituted or unsubstituted heteroaryl
wherein
R7 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
and
R8 is a member selected from substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
Rc is a member selected from H and substituted or unsubstituted C1-C5 alkyl;
Rd is a member selected from R16 and CH2R16
wherein
R16 is a member selected from C(O)R18,
wherein
R18 is a member selected from OR21, NR19R20, and NR19SO2R20
wherein
R21 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted aryl;
R19 is a member selected from H and substituted or unsubstituted C1-C5 alkyl;
and
R20 is a member selected from H, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
and
R19 and R20 can be optionally joined, together with the atoms to which they are attached, to form a 6 membered ring;
and
Rd′ is a member selected from substituted or unsubstituted C1-C5 alkyl and substituted or unsubstituted C3-C6 cycloalkyl.

25 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/703,610Filed 10 Feb 2010
Priority: 4 Apr 2005
Published: 10 Jun 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 405/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
A61P 7/00
Drugs for disorders of the blood or the extracellular fluid
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
A61P 9/00
Drugs for disorders of the cardiovascular system

Family

Application60/668,325Us provisional application · filed 4 Apr 2005
Application11/398,438Continuation · filed 4 Apr 2006
Application12/359,490Continuation · filed 26 Jan 2009
Application12/703,610Continuation
US 2007/0105832 A1Published application
US 2009/0143351 A1Published application
US 7,501,404 B2Related patent
US 2010/0144698 A1This patent

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