US2007185179A1PendingUtilityA1
New compounds
Est. expiryFeb 7, 2026(expired)· nominal 20-yr term from priority
A61P 9/10A61P 25/06A61P 29/00A61P 25/02A61P 3/04A61P 35/00A61P 25/00A61P 25/04A61P 1/04A61P 17/06A61P 17/02A61P 19/02A61P 11/06A61P 1/00A61P 13/10A61P 19/10A61P 11/00C07D 209/38C07D 487/10A61K 31/4188
47
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Claims
Abstract
The present invention relates to new compounds of formula I, where R 1 and R 2 are independently halo or C 1-3 haloalkyl, X is ethenyl or ethynyl, or a salt thereof.
Claims
exact text as granted — not AI-modified1 . A compound having the formula I:
where R 1 and R 2 are independently halo or C 1-3 haloalkyl,
X is ethenyl or ethynyl,
or a salt thereof,
with the proviso that it is not 1′-[(2E)-3-(3,4-dichlorophenyl)prop-2-en-1-yl]-2H,5H-spiro[imidazolidine-4,3′-indole]-2,2′,5(1′H)-trione in racemic form.
2 . A compound or salt thereof according to claim 1 , where R 1 is halo and R 2 is C 1-3 haloalkyl.
3 . A compound or salt thereof according to claim 1 , where R 1 is chloro or fluoro and R 2 is C 1-3 chloroalkyl or C 1-3 fluoroalkyl.
4 . A compound or salt thereof according to claim 1 , where R 1 is chloro.
5 . A compound or salt thereof according to claim 1 , where R 1 and R 2 are chloro.
6 . A compound or salt thereof according to claim 1 , where X is
7 . A compound or salt thereof according to claim 1 , where X is ethynyl.
8 . A salt of a compound according to claim 1 .
9 . A salt according to claim 8 , which is a pharmaceutically acceptable salt.
10 . A compound according to claim 1 selected from the group consisting of
1′-[(2E)-3-(3-chloro-4-trifluorophenyl)prop-2-en-1-yl]-2H,5H-spiro [imidazolidine-4,3′-indole]-2,2′,5(1′H)-trione and 1′-[3-(3,4-dichlorophenyl)prop-2-yn-1-yl]-2H,5H-spiro[imidazolidine-4,3′-indole]-2,2′,5(1′H)-trione.
11 . A compound or salt thereof according to claim 1 , for use as a medicament.
12 . A compound or salt thereof according to claim 1 , for use as a medicament for treatment of VR1 mediated disorders.
13 . A compound having the formula I:
where R 1 and R 2 are independently halo or C 1-3 haloalkyl,
X is ethenyl or ethynyl,
or a pharmaceutically acceptable salt thereof,
for use as a medicament for treatment of VR1 mediated disorders.
14 . Use of a compound having the formula I:
where R 1 and R 2 are independently halo or C 1-3 haloalkyl,
X is ethenyl or ethynyl,
or a salt thereof,
in the manufacture of a medicament,
with the proviso that the compound is not 1′-[(2E)-3-(3,4-dichlorophenyl)prop-2-en-1-yl]-2H,5H-spiro[imidazolidine-4,3′-indole]-2,2′,5 (1′H)-trione in racemic form.
15 . Use of a compound having the formula I:
where R 1 and R 2 are independently halo or C 1-3 haloalkyl,
X is ethenyl or ethynyl,
or a salt thereof,
in the manufacture of a medicament for treatment of VR1 mediated disorders.
16 . The use according to claim 14 in the manufacture of a medicament for treatment of VR1 mediated disorders.
17 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment of acute and chronic pain disorders.
18 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment of acute and chronic neuropathic pain.
19 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment of acute and chronic inflammatory pain.
20 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment acute and chronic nociceptive pain.
21 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment of low back pain, post-operative pain, visceral pains like chronic pelvic pain, cystitis, including interstitial cystitis and pain related thereto, ischeamic, sciatia, multiple sclerosis, arthritis, fibromyalgia, pain and other signs and symptoms associated with psoriasis, pain and other signs and symptoms associated with cancer, emesis, urinary incontinence, hyperactive bladder, HIV neuropathy, gastro-esophageal reflux disease (GERD), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and/or pancreatitis, including signs and/or symptoms related to said diseases.
22 . The use according claim 14 or 15 in the manufacture of a medicament for treatment of osteoarthritis, rheumatoid arthritis, asthma, cough, chronic obstructive lung disease, specifically chronic obstructive pulmonary disease (COPD) and emphysema, lung fibrosis, and interstitial lung disease, including signs and/or symptoms related to said diseases.
23 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment of respiratory diseases.
24 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment of obesity and/or migraine.
25 . The use according to claim 14 or 15 in the manufacture of a medicament for treatment of burn induced pain and/or inflammatory pain resulting from burn injuries.
26 . A method of treatment of VR1 mediated disorders and for treatment of acute and chronic pain disorders, acute and chronic neuropathic pain and acute and chronic inflammatory pain, and/or respiratory diseases, comprising administrering to a mammal, including man in need of such treatment, a therapeutically effective amount of a compound or salt thereof according to claim 1 .
27 . A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound or salt thereof according to claim 1 , in association with one or more pharmaceutically acceptable diluents, excipients and/or inert carriers.
28 . The pharmaceutical composition according to claim 27 , for use in the treatment of VR1 mediated disorders and for treatment of acute and chronic pain disorders such as acute or chronic neuropathic pain and acute or chronic inflammatory pain; and/or respiratory diseases.
29 . A process for preparing a compound of formula I according to claim 1 , comprising:
Reaction of an optionally protected compound of formula III i) with KCN and (NH4) 2 CO 3 in at eleveted temperature in a suitable solvent, and thereafter optionally: ii) converting a compound of the formula I into another compound of the formula I; and/or iii) removing any protecting groups; and/or iv) forming a pharmaceutically acceptable salt.
30 . A substantially pure single enantiomer having the formula II:
where R 1 and R 2 are independently halo or C 1-3 haloalkyl,
X is ethenyl or ethynyl,
or a salt thereof.
31 . An enantiomer or salt thereof according to claim 30 , where R 1 is halo and R 2 is C 1-3 haloalkyl.
32 . An enantiomer or salt thereof according to claim 30 , where R 1 is chloro or fluoro and R 2 is C 1-3 chloroalkyl or C 1-3 fluoroalkyl.
33 . An enantiomer or salt thereof according to claim 30 , where R 1 is chloro.
34 . An enantiomer or salt thereof according to claim 30 , where R 1 and R 2 are chloro.
35 . An enantiomer or salt thereof according to claim 30 , where X is
36 . An enantiomer or salt thereof according to claim 30 , where X is ethynyl.
37 . A salt of an enantiomer according to claim 30 .
38 . A salt according to claim 37 , which is a pharmaceutically acceptable salt.
39 . An enantiomer according to claim 30 selected from the group consisting of
(4R)-1′-[(2E-3-(3,4-dichlorophenyl)prop-2-en-1-yl]-2H,5H-spiro [imidazolidine-4,3′-indole]-2,2′,5(1′H)-trione, (4R)-1′-[(2E)-3-(3-chloro-4-trifluorophenyl)prop-2-en-1-yl]-2H,5H-spiro [imidazolidine-4,3′-indole]-2,2′,5(1′H)-trione, and (4R)-1′-[3-(3,4-dichlorophenyl)prop-2-yn-1-yl]-2H,5H-spiro[imidazolidine-4,3′-indole]-2,2′,5(1′H)-trione.
40 . The enantiomer or salt thereof according to any one of claims 30 to 39 , for use as a medicament.
41 . The enantiomer or salt thereof according to any one of claims 30 to 39 , for use as a medicament for treatment of VR1 mediated disorders.
42 . Use of an enantiomer or salt thereof according to any one of claims 30 to 39 , in the manufacture of a medicament.
43 . Use of an enantiomer or salt thereof according to any one of claims 30 to 39 , in the manufacture of a medicament for treatment of VR1 mediated disorders.
44 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment of acute and chronic pain disorders.
45 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment of acute and chronic neuropathic pain.
46 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment of acute and chronic inflammatory pain.
47 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment acute and chronic nociceptive pain.
48 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment of low back pain, post-operative pain, visceral pains like chronic pelvic pain, cystitis, including interstitial cystitis and pain related thereto, ischeamic, sciatia, multiple sclerosis, arthritis, fibromyalgia, pain and other signs and symptoms associated with psoriasis, pain and other signs and symptoms associated with cancer, emesis, urinary incontinence, hyperactive bladder, HIV neuropathy, gastro-esophageal reflux disease (GERD), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and/or pancreatitis, including signs and/or symptoms related to said diseases.
49 . The use according claim 42 or 43 in the manufacture of a medicament for treatment of osteoarthritis, rheumatoid arthritis, asthma, cough, chronic obstructive lung disease, specifically chronic obstructive pulmonary disease (COPD) and emphysema, lung fibrosis, and interstitial lung disease, including signs and/or symptoms related to said diseases.
50 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment of respiratory diseases.
51 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment of obesity and/or migraine.
52 . The use according to claim 42 or 43 in the manufacture of a medicament for treatment of burn induced pain and/or inflammatory pain resulting from burn injuries.
53 . A method of treatment of VR1 mediated disorders and for treatment of acute and chronic pain disorders, acute and chronic neuropathic pain and acute and chronic inflammatory pain, and/or respiratory diseases, comprising administrering to a mammal, including man in need of such treatment, a therapeutically effective amount of an enantiomer or salt thereof according to claim 30 .
54 . A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of an enantiomer or salt thereof according to claim 30 , in association with one or more pharmaceutically acceptable diluents, excipients and/or inert carriers.
55 . The pharmaceutical composition according to claim 54 , for use in the treatment of VR1 mediated disorders and for treatment of acute and chronic pain disorders such as acute or chronic neuropathic pain and acute or chronic inflammatory pain; and/or respiratory diseases.
56 . A process for preparing an enantiomer of formula II according to claim 30 , comprising:
Reaction of an optionally protected compound of formula III i) with KCN and (NH4) 2 CO 3 in eleveted temperature in a suitable solvent, and thereafter separation of said enantiomer from the racemic mixture by supercritical fluid chromatography.
57 . A compound selected from the group consisting of
1-Allyl-1H-indole-2,3-dione, 1-[(2E)-3-(3,4-dichlorophenyl)prop-2-en-1-yl]-1H-indole-2,3-dione, 1-{(2E)-3-[4-chloro-3-(trifluoromethyl)phenyl]prop-2-en-1-yl}-1H-indole-2,3-dione, 1-prop-2-yn-1-yl-1H-indole-2,3-dione, and 1-[3-(3,4-dichlorophenyl)prop-2-yn-1-yl]-1H-indole-2,3-dione
58 . Use of compounds according to claim 57 as intermediates in the preparation of a compound according to claim 1 .
59 . Use of compounds according to claim 57 as intermediates in the preparation of an enantiomer according to claim 30 .
60 . A process for preparing a compound of formula III
where R 1 and R 2 are independently halo or C 1-3 haloalkyl,
X is ethenyl or ethynyl, comprising:
Reaction of an optionally protected compound of formula IV
with
where HAL is an halogen atom, in the presence of a suitable palladium catalyst, such as Pd(P(t-Bu) 3 ) 2 or Pd(OAc) 2 , in a suitable solvent,
and thereafter optionally:
ii) converting the intermediate of formula III into another intermediate of formula III; and/or
iii) removing any protecting groups.Join the waitlist — get patent alerts
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