Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-03-12
2004-08-03
Rao, Deepak (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S262100, C514S263220, C514S263300, C544S184000, C544S262000, C544S265000, C544S276000
Reexamination Certificate
active
06770645
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to pharmaceutically useful compounds which inhibit cyclic guanosine 3′,5′-monophosphate phosphodiesterases (cGMP PDEs). More notably, the compounds of the invention are potent inhibitors of type 5 cyclic guanosine 3′,5′-monophosphate phosphodiesterase (cGMP PDE5) and are selective over other phosphodiesterases, including PDE6. The compounds of the invention therefore have utility in a variety of therapeutic areas.
The compounds of the invention are of value for the curative or prophylactic treatment of mammalian sexual disorders. In particular, the compounds are of value in the treatment of mammalian sexual dysfunctions such as male erectile dysfunction (MED), impotence, female sexual dysfunction (FSD), clitoral dysfunction, female hypoactive sexual desire disorder, female sexual arousal disorder, female sexual pain disorder or female sexual orgasmic dysfunction (FSOD) as well as sexual dysfunction due to spinal cord injury or selective serotonin re-uptake inhibitor (SSRI) induced sexual dysfunction but, clearly, will be useful also for treating other medical conditions for which a potent and selective cGMP PDE5 inhibitor is indicated. Such conditions include premature labour, dysmenorrhoea, benign prostatic hyperplasia (BPH), bladder outlet obstruction, incontinence, stable, unstable and variant (Prinzmetal) angina, hypertension, pulmonary hypertension, chronic obstructive pulmonary disease, coronary artery disease, congestive heart failure, atherosclerosis, conditions of reduced blood vessel patency, e.g. post-percutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, stroke, nitrate induced tolerance, bronchitis, allergic asthma, chronic asthma, allergic rhinitis, diseases and conditions of the eye such as glaucoma, optic neuropathy, macular degeneration, elevated intra-occular pressure, retinal or arterial occulsion and diseases characterised by disorders of gut motility, e.g. irritable bowel syndrome (IBS).
Further medical conditions for which a potent and selective cGMP PDE5 inhibitor is indicated, and for which treatment with compounds of the present invention may be useful, include pre-eclampsia, Kawasaki's syndrome, nitrate tolerance, multiple sclerosis, diabetic nephropathy, neuropathy including autonomic and peripheral neuropathy and in particular diabetic neuropathy and symptoms thereof (e.g. gastroparesis), peripheral diabetic neuropathy, Alzheimer's disease, acute respiratory failure, psoriasis, skin necrosis, cancer, metastasis, baldness, nutcracker oesophagus, anal fissure, haemorrhoids, hypoxic vasoconstriction, hypoxic vasoconstriction, diabetes, type 2 diabetes mellitus, the insulin resistance syndrome, insulin resistance, impaired glucose tolerance, as well as the stabilisation of blood pressure during haemodialysis.
Particularly preferred sexual disorders include MED and FSD.
DISCLOSURE OF THE INVENTION
According to the present invention, there is provided compounds of general formula I:
or a pharmaceutically or veterinarily acceptable salt and/or solvate, polymorph or pro-drug thereof, wherein
Y represents C or N, with N being in at least one, but not more than two, of the positions marked by Y;
X represents CH or N;
R
1
, R
2
and R
3
where present and attached to nitrogen independently represent H, C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl;
R
1
, R
2
and R
3
where present and attached to carbon independently represent H, halo, cyano, nitro, OR
6
, OC(O)R
6
, C(O)R
6
, C(O)OR
6
, NR
6
C(O)NR
7
R
8
, NR
6
(O)OR
6
OC(O)NR
7
R
8
, C(O)NR
9
R
10
, NR
9
R
10
, SO
2
NR
9
R
10
, SO
2
R
11
, C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl;
wherein when R
1
and R
2
are present they may optionally be connected via a C—C, C—N or C—O bond;
wherein when R
2
and R
3
are present they may optionally be connected via a C—C, C—N or C—O bond;
R
4
represents H, C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl;
R
5
represents C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl;
wherein when R
1
, R
2
and R
3
, where present, or R
4
or R
5
is a C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl and C
1
-C
6
alkylaryl group, such C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl and C
1
-C
6
alkylaryl group is optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
6
, OC(O)R
6
, C(O)R
6
, C(O)OR
6
, NR
6
C(O)NR
7
R
8
, NR
6
C(O)OR
6
, OC(O)NR
7
R
8
, C(O)NR
9
R
10
, NR
9
R
10
, SO
2
NR
9
R
10
, SO
2
R
11
, C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl which latter five substituent groups are all optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
12
, OC(O)R
12
, C(O)R
12
, C(O)OR
12
, NR
12
C(O)NR
13
R
14
, NR
12
C(O)OR
12
, OC(O)NR
13
R
14
, C(O)NR
15
R
16
, NR
15
R
16
, SO
2
NR
15
R
16
, SO
2
R
17
;
R
6
represents H, C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl which latter five substituent groups are all optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
12
, OC(O)R
12
, C(O)R
12
, C(O)OR
12
, NR
12
C(O)NR
13
R
14
, NR
12
C(O)OR
12
, OC(O)NR R
14
, C(O)NR
15
R
16
, NR
15
R
16
, SO
2
NR
15
R
16
, SO
2
R
17
;
R
7
and R
8
independently represent H, C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl which latter five substituent groups are all optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
12
, OC(O)R
12
, C(O)R
12
, C(O)OR
12
, NR
12
C(O)NR
13
R
14
, NR
12
C(O)OR, OC(O)NR
13
R
14
, C(O)NR
15
R
16
, NR
15
R
16
, SO
2
NR
15
R
16
, SO
2
R
17
; or
R
7
and R
8
together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
12
, OC(O)R
12
, C(O)R
12
. C(O)OR
12
, NR
12
C(O)NR
13
R
14
, NR
12
C(O)OR
12
, OC(O)NR
13
R
14
, C(O)NR
15
R
16
, NR
15
R
16
, SO
2
NR
15
R
16
, SO
2
R
17
;
R
9
and R
10
independently represent H, C(O)R
6
, SO
2
R
11
, C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl which latter five substituent groups are all optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
12
, OC(O)R
12
, C(O)R
12
, C(O)OR
12
, NR
12
C(O)NR
13
R
14
, NR
12
C(O)OR
12
, OC(O)NR
13
R
14
, C(O)NR
15
R
16
, NR
15
R
16
, SO
2
NR
15
R
16
, SO
2
R
17
; or
R
9
and R
10
together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
12
, OC(O)R
12
, C(O)R
12
, C(O)OR
12
, NR
12
C(O)NR
13
R
14
, NR
12
C(O)OR
12
, OC(O)NR
13
R
14
, C(O)NR
15
R
16
, NR
15
R
16
, SO
2
NR
15
R
16
, SO
2
R
17
;
R
11
represents C
1
-C
6
alkyl, Het, C
1
-C
6
alkylHet, aryl or C
1
-C
6
alkylaryl which latter five substituent groups are all optionally substituted and/or terminated with one or more substituents selected from halo, cyano, nitro, OR
12
, OC(O)R
12
, C(O)R
12
, C(O)OR
12
, NR
12
C(O)NR
13
R
14
, NR
12
C(O)OR
12
, OC(O)NR
13
R
14
, C(O)NR
15
R
16
, NR
15
R
16
, SO
2
NR
15
R
16
, SO
2
R
17
;
R
12
represents H or C
1
-C
6
alkyl;
R
13
and R
14
independently represent H or C
1
-C
6
alkyl; or
R
13
and R
14
together with the nitrogen atom to which they are bound can form a heterocyclic ring;
R
15
and R
16
independently represent H, C(O)R
12
, SO
2
R
17
or C
1
-C
6
alkyl; or
R
15
and R
16
together with the nitrogen atom to which they are bound can form a heterocyclic ring;
R
17
represents C
1
-C
6
alkyl;
Het represents an optionally substituted four- to twelve-membered heterocyclic group, which group contains one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof and with the proviso that when R
5
is Het, said Het is C-li
Denton Stephen Martin
Kemp Mark Ian
Newman Sandra Dora
Rawson David James
Benson Gregg C.
Olson A. Dean
Pfizer Inc.
Rao Deepak
Richardson Peter C.
LandOfFree
Pharmaceutically active compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutically active compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutically active compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3324172