# US 2013/0158035 A1 · Antimetastatic compounds

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- Number: US 2013/0158035 A1
- Document ID: US20130158035A1
- Status: Published application
- Kind: A1
- Application number: 13/818,272
- Filed: 2011-08-23
- Published: 2013-06-20
- Earliest claimed: 2010-08-24
- Assignees: Brigham Young University
- Inventors: Marc Hansen
- Web page: https://patentgrep.com/patent/US20130158035A1

## CPC

- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/381: having five-membered rings
- A61K 31/4015: having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
- A61K 31/402: 1-aryl substituted, e.g. piretanide
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/4704: 2-Quinolinones, e.g. carbostyril
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/473: ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
- A61K 31/4741: condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
- A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53})
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Screening methods for identifying compounds and compounds and pharmaceutical compositions for treating and preventing cancer are disclosed. The compounds affect signal transduction downstream of the MET receptor.

## Claims

### Claim 1

A pharmaceutical composition comprising a compound of formula I-I
wherein W1 is selected from O, OCH2, OCH3, OCH2CH3, CH2, and CH3;
W2 is selected from O, OCH2, OCH3, OCH2CH3, CH2, and CH3;
W3 is selected from H and OCH3;
Z if present is alkylene;
each R if present is independently selected from halogen, hydroxyl, alkoxy, benzylalkoxy, alkyl, CF3, OCF3, nitro, fused aryl, fused heterocycle, S-alkyl, NH2, NH-alkyl, and N(alkyl)2;
n is an integer of from 0 to 3; and
pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

A pharmaceutical composition according to claim 1, wherein the compound is of formula I:
wherein W1 is selected from O, OCH2, OCH3, OCH2CH3, CH2, and CH3;
W2 is selected from O, OCH2, OCH3, OCH2CH3, CH2, and CH3;
Z if present is alkylene;
each R if present is independently selected from halogen, hydroxyl, alkoxy, benzylalkoxy, alkyl, CF3, OCF3, nitro, fused aryl, fused heterocycle, S-alkyl, NH2, NH-alkyl, and N(alkyl)2;
n is an integer of from 0 to 3; and
pharmaceutically acceptable salts thereof.

### Claim 3 (depends on 1)

A pharmaceutical composition according to claim 1, wherein the compound is of formula Ia
wherein each R if present is independently selected from halogen, hydroxyl, alkoxy, benzylalkoxy, alkyl, CF3, OCF3, nitro, fused aryl, fused heterocycle, S-alkyl, NH2, NH-alkyl, and N(alkyl)2;
n is an integer of from 0 to 3; and
pharmaceutically acceptable salts thereof.

### Claim 4 (depends on 1)

A pharmaceutical composition according to claim 1, wherein the compound is of formula Ib
wherein each R if present is independently selected from halogen, hydroxyl, alkoxy, benzylalkoxy, alkyl, CF3, OCF3, nitro, fused aryl, fused heterocycle, S-alkyl, NH2, NH-alkyl, and N(alkyl)2;
n is an integer of from 0 to 3; and
pharmaceutically acceptable salts thereof.

### Claim 5 (depends on 1)

A pharmaceutical composition according to claim 1, wherein each of W1 and W2 is OCH3, and W3 is selected from H and OCH3;
each R is alkoxy;
n is an integer of from 1 to 3; and
pharmaceutically acceptable salts thereof.

### Claim 6 (depends on 1)

A pharmaceutical composition according to claim 1, wherein the compound is of formula Id:
wherein each R if present is independently selected from halogen, hydroxyl, alkoxy, CF3, fused aryl, fused heterocycle;
n is an integer of from 0 to 2; and
pharmaceutically acceptable salts thereof.

### Claim at position 7

7-11. (canceled)

### Claim 12 (depends on 1)

A pharmaceutical composition according to claim 1, wherein R1 is halogen, and pharmaceutically acceptable salts thereof.

### Claim 13 (depends on 1)

A pharmaceutical composition according to claim 1, wherein R1 is hydroxyl, and pharmaceutically acceptable salts thereof.

### Claim 14 (depends on 1)

A pharmaceutical composition according to claim 1, wherein R1 is alkoxy, and pharmaceutically acceptable salts thereof.

### Claim at position 11

15-16. (canceled)

### Claim 17 (depends on 1)

A pharmaceutical composition according to claim 1, wherein R1 is alkyl, and pharmaceutically acceptable salts thereof.

### Claim at position 13

18-19. (canceled)

### Claim 20 (depends on 1)

A pharmaceutical composition according to claim 1, wherein R1 is CF3, and pharmaceutically acceptable salts thereof.

### Claim 21

(canceled)

### Claim 22 (depends on 1)

A pharmaceutical composition according to claim 1, wherein R1 is fused aryl, and pharmaceutically acceptable salts thereof.

### Claim 23

(canceled)

### Claim 24 (depends on 1)

A pharmaceutical composition according to claim 1, wherein R1 is a fused heterocycle, and pharmaceutically acceptable salts thereof.

### Claim at position 19

25-37. (canceled)

### Claim 38 (depends on 6)

A pharmaceutical composition according to claim 6, wherein each R is selected from halogen.

### Claim at position 21

39-40. (canceled)

### Claim 41 (depends on 1)

A method of inhibiting cellular responses to MET receptor signaling by administering a pharmaceutical composition according to claim 1.

### Claim 42 (depends on 1)

A method of preventing or treating cancer comprising administering a compound or pharmaceutical composition according to claim 1.

### Claim 43

A pharmaceutical composition comprising a compound of formula A-I
wherein W is selected from O, S, and —C(R4)═C(R5)—;
R1 is selected from alkyl, —C(O)NH2—, and H
R2 is selected from alkyl, halogen, morpholino, and H;
R3 is selected from CO2H, halogen, and H;
R4, if present, is selected from halogen, hydroxyl, nitro, H, or together with R5 form a fused phenyl ring;
R5, if present, is selected from halogen, alkoxy, H, or together with one of R4 and R6 form a fused phenyl ring;
R6 is selected from alkyl, alkoxy, OCH2C≡CH, halogen, and H;
R7 is selected from alkoxy, halogen, and H;
Z is selected from —N═C— and —NH—CH2—;
pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable carrier.

### Claim at position 25

44-66. (canceled)

### Claim 67

A pharmaceutical composition comprising a compound of formula B-I
wherein A is selected from —C(O)NH—, —NHC(O)—, —NHC(O)CH2—O—, —NHS(O)2—, —S(O)2NH—, —OCH2C(O)NH—, and —O(O)—;
W is selected from N, C—H, C—R1, C—R2, and C—R3;
each of R1, R2, and R3 if present is independently selected from halo, alkyl, alkoxy, optionally substituted aryl, hydroxyl;
each of R4 and R5 if present is selected from halo, alkyl, alkoxy, C(O)alkyl, C(O)NH2, NH(CO)alkyl, NHalkyl, N(alkyl)2, NH(aryl), nitro, C(O)aryl, C(O)-optionally substituted heterocycle, optionally substituted heterocycle; and
pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable carrier.

### Claim at position 27

68-134. (canceled)

### Claim 135

A pharmaceutical composition comprising a compound of formula C-I
wherein R1 is selected from alkyl;
R2 is selected from aryl optionally substituted with one alkoxy and heteroaryl;
R3 is selected from alkyl, cycloalkyl, alkylcycloalkyl optionally substituted with alkyl, alkylheterocyclyl, and alkylaryl optionally substituted with alkyl;
pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable carrier.

### Claim at position 29

136-156. (canceled)