Back to results
US 7,351,711 B2Granted
Tricyclic indanyls as integrin inhibitors
AssigneeJanssen Pharmaceutical N.V.
InventorsWilliam A. Kinney, Diane K. Luci, Bruce E. Maryanoff
Life of this patent
Estimating the term…
Abstract
The present invention is directed to substituted indanyl compounds of Formula (I): Useful for treating integrin-mediated disorders such as, but not limited to unstable angina, thromboemboic disorders, osteoporosis, growth and metastasis of malignant tumors, diabetic retinopathy, arthritis, viral disease and surgical adhesions.
Claims29
A compound of Formula (I):
- wherein:
- R is selected from the group consisting of hetercyclyl and heteroaryl;
- R1 is one to two substituents selected from the group consisting of hydrogen, C1-4alkyl, C1-4alkoxy, hydroxy, —NRARB, and halogen;
- wherein alkyl and alkoxy are optionally substituted on a terminal carbon one to three substituents independently selected from the group halogen, hydroxy, and —NRARB;
- wherein RA and RB are substituents independently selected from hydrogen or C1-6alkyl;
- R2 is one to two substituents independently selected from the group consisting of hydrogen, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-4alkoxy, —NRCRD, hydroxy, and halogen;
- wherein alkyl, alkenyl, alkynyl, and alkoxy are optionally substituted on a terminal carbon with one to three substituents independently selected from the group halogen, hydroxy, C1-4alkoxy, and —NRCRD;
- wherein RC and RD are substituents independently selected from hydrogen or C1-6alkyl;
- RC and RD are optionally taken together with the atoms to which they are attached to form a five to seven membered monocyclic ring;
- Z is selected from the group consisting of —CH2— and —CH—;
- A is selected from the group consisting of aryl, —CH(CH2)1-3—, and —(CH2)1-3—;
- provided that when A is —CH(CH2)1-2— and Z is —CH— then a double bond is formed between A and Z;
- B is —NH— when optionally present;
- m and n are integers from 1 to 3;
- X is selected from the group consisting of O, S, and two hydrogen atoms;
- U is independently selected from the group consisting of —CH—, N, and S, provided that no more than one U represents S or N;
- and that U can only be S when W is not present;
- W is selected from the group consisting of —CH— and N when optionally present;
- and enantiomers, diastereomers, tautomers, or pharmaceutically acceptable salts thereof.
16 more elements
Compounds of Formula (II):
- wherein R, R1, B, A, m, n, and R2 are dependently selected from the group consisting of:
- Stereo
- Cpd
- chem.
- R
- R1
- B
- A
- m
- n
- R2
- 1
- cis
- 1,4,5,6,-tetrahydro-
- H
- NH
- 1,3-
- 2
- 1
- H
- pyrimidin-2-yl
- phenyl
- 2
- trans
- 1,4,5,6,-tetrahydro-
- H
- NH
- 1,3-
- 2
- 1
- H
- pyrimidin-2-yl
- phenyl
- 3
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)2—
- 2
- 1
- H
- [1,8]naphthyridine-2-yl
- 4
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 2
- 1
- H
- [1,8]naphthyridine-2-yl
- 5
- racemic
- 1,4,5,6,-tetrahydro-
- OH
- NH
- 1,3-
- 2
- 1
- H
- pyrimidin-2-yl
- phenyl
- 6
- cis
- Pyridin-2-yl
- H
- NH
- —(CH2)2—
- 2
- 1
- H
- 7
- trans
- Pyridin-2-yl
- H
- NH
- —(CH2)2—
- 2
- 1
- H
- 8
- racemic
- Pyridin-2-yl
- H
- NH
- —(CH2)3—
- 2
- 1
- H
- 9
- cis
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)2—
- 1
- 2
- H
- [1,8]naphthyridine-2-yl
- 10
- trans
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)2—
- 1
- 2
- H
- [1,8]naphthyridine-2-yl
- 11
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 2
- H
- [1,8 ]naphthyridine-2-yl
- 12
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- H
- [1,8]naphthyridine-2-yl
- 13
- cis
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- H
- [1,8 ]naphthyridine-2-yl
- 14
- trans
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- H
- [1,8 ]naphthyridine-2-yl
- 15
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)2—
- 1
- 1
- H
- [1,8 ]naphthyridine-2-yl
- 16
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- F
- [1,8 ]naphthyridine-2-yl
168 more elements
The compound of Formula (II):
- The compound of Formula (II) wherein R, R1, B, A, m, n, and R2 are dependently selected from the group consisting of:
- Cpd
- Stereo chem.
- R
- R1
- B
- A
- m
- n
- R2
- 1
- cis
- 1,4,5,6,-tetrahydro-
- H
- NH
- 1,3-
- 2
- 1
- H
- pyrimidin-2-yl
- phenyl
- 2
- trans
- 1,4,5,6,-tetrahydro-
- H
- NH
- 1,3-
- 2
- 1
- H
- pyrimidin-2-yl
- phenyl
- 3
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)2—
- 2
- 1
- H
- [1,8]naphthyridine-2-yl
- 4
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 2
- 1
- H
- [1,8]naphthyridine-2-yl
- 12
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- H
- [1,8]naphthyridine-2-yl
- 13
- cis
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- H
- [1,8]naphthyridine-2-yl
- 14
- trans
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- H
- [1,8]naphthyridine-2-yl
- 15
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)2—
- 1
- 1
- H
- [1,8]naphthyridine-2-yl
- 16
- racemic
- 5,6,7,8-tetrahydro-
- H
- absent
- —(CH2)—
- 1
- 1
- F
- [1,8]naphthyridine-2-yl
99 more elements
Dependencies are inferred from the claim text.