sGC stimulators
Inventors
Kim, Charles • Nakai, Takashi • Lee, Thomas Wai-Ho • Moore, Joel • Perl, Nicholas Robert • Rohde, Jason
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9061030-B2
Publication Date
2015-06-23
Expiration Date
Abstract
Compounds of Formula IA and Formula IB are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.
Core Innovation
The invention relates to a compound according to Formula IA or Formula IB, or a pharmaceutically acceptable salt thereof. Ring B is defined as a phenyl or a 6-membered heteroaryl ring having 1 or 2 nitrogen ring atoms, with n selected from 0 to 3 and each J_B independently selected from halogen, —CN, —NO2, a C1-6 aliphatic, —OR_B, or a C3-8 cycloaliphatic group, each optionally and independently substituted with up to 3 instances of R3.
The compound further defines ring D as the 5-membered ring heteroaryl of Formula IB or the 6-membered heteroaryl ring of Formula IA substituted by m instances of J_D. X is selected from N or C, and each Y is independently selected from C, N, O or S, with a minimum of 0 and maximum of 3 instances of Y simultaneously being N, O or S and the remaining instances being C. Each J_D substituent on carbon ring atoms and nitrogen ring atoms is independently selected from the listed functional group classes and ring or aliphatic options, with alternative ring-closure provisions forming 4 to 8-membered heterocyclic rings, 5-membered heteroaryl rings, fused heterocycles, and fused ring D structures.
The invention also defines ring C selection and substitution, where ring C is a phenyl ring, a monocyclic 5 or 6-membered heteroaryl ring, a bicyclic 8 to 10-membered heteroaryl ring, a monocyclic 3 to 10-membered cycloaliphatic ring, or a monocyclic 4 to 10-membered heterocycle, with corresponding constraints on J_C and R_H and optional fused-ring formation when two J_C groups are linked to vicinal ring atoms. The disclosure provides a condition that the compound is not one of the compounds represented below.
Claims Coverage
The consolidated input provides one independent claim, clm-00001, covering a compound according to Formula IA or Formula IB, or a pharmaceutically acceptable salt thereof. The claim centers on four main inventive features: ring B, ring D, ring C, and exclusion of listed represented compounds, together with defined integer variables n and m, heteroatom pattern constraints, substituent selection rules, and alternative ring-formation options.
Compound according to Formula IA or Formula IB
A compound according to Formula IA or Formula IB, or a pharmaceutically acceptable salt thereof, wherein ring B is a phenyl or a 6-membered heteroaryl ring having 1 or 2 nitrogen ring atoms, n is selected from 0 to 3, and each J_B is independently selected from halogen, —CN, —NO2, a C1-6 aliphatic, —OR_B, or a C3-8 cycloaliphatic group, each optionally and independently substituted with up to 3 instances of R3.
Ring D substitution pattern with heteroatom-defined Y and m instances of J_D
Ring D is the 5-membered ring heteroaryl of Formula IB or the 6-membered heteroaryl ring of Formula IA substituted by m instances of J_D, where X is selected from N or C; each Y is independently selected from C, N, O or S with a minimum of 0 and maximum of 3 instances of Y simultaneously being N, O or S and the remaining instances being C; and m is an integer selected from 0 to 3.
Alternative fused-ring and linking constraints for J_D and ring C
The compound includes alternatives in which two instances of R_D linked to the same nitrogen atom of J_D, or one instance of R_D linked to a carbon, oxygen or sulfur atom of J_D and one instance of R_d linked to a nitrogen atom of the same J_D, form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring. Ring C is defined as a phenyl ring, a monocyclic 5 or 6-membered heteroaryl ring, a bicyclic 8 to 10-membered heteroaryl ring, a monocyclic 3 to 10-membered cycloaliphatic ring, or a monocyclic 4 to 10-membered heterocycle, with corresponding substitution constraints and optional fused-ring formation when two J_C groups are linked to vicinal ring atoms.
Exclusion of listed represented compounds
The compound is provided with the condition that the compound is not one of the compounds represented below.
The claim coverage centers on the compound defined by Formula IA or IB, with specified ring B and ring D substitution patterns, defined heteroatom constraints for X and Y, ring C selection and substitution, alternative ring-linking constructions, and an explicit exclusion of compounds represented below.
Stated Advantages
The compounds are NO-independent and heme-dependent sGC stimulators.
Documented Applications
Therapeutic use for peripheral/cardiovascular disorders and urogenital disorders is described, including pulmonary hypertension, hypertension, heart failure, atherosclerosis, inflammation, thrombosis, renal fibrosis/failure, liver cirrhosis, and erectile dysfunction.
Interested in licensing this patent?