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US 2025/0049765 A1Published application
Bicyclo [3.2.0] heptane bis(amide) rxfp1 agonists
OwnerAndrew K. Dilger, Leon M. Smith ll +2inventors
InventorsAndrew K. Dilger, Leon M. Smith ll, Michael J. Orwat, Donald J.P. Pinto
Life of this patent
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Abstract
The disclosure relates to compounds of Formula (I), which are RXFP1 receptor agonists, compositions containing them, and methods of using them, for example, in the treatment of heart failure, fibrotic diseases, and related diseases such as lung disease (e.g., idiopathic pulmonary fibrosis), kidney disease (e.g., chronic kidney disease), or hepatic disease (e.g., non-alcoholic steatohepatitis and portal hypertension).
Claims11
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- is an optional bond;
- R1 is H or halo;
- or R1 and R1 together form a phenyl ring;
- R2 is halo, C1-4 alky, OH, or —OC1-4 alkyl substituted with 0-4 halo, OH, or —OC1-4 alkyl;
- R4a is halo;
- R4b is C1-4 alkyl substituted with 0-4 halo;
- R5 is C2-8 alkenyl substituted with 0-3 R6 and 0-2 R7, C2-8 alkynyl substituted with 0-3 R6 and 0-2 R7, C6-12 aryl substituted with 0-3 R6 and 0-2 R7, or a 3- to 12-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(═O)p, N and NR10 substituted with 0-3 R6 and 0-1 R7;
- wherein said heterocyclyl is bonded to the phenyl moiety through a carbon or nitrogen atom;
- R6 is halo, —O, —OH, —OC1-4 alkyl, or C1-4 alkyl substituted with 0-2 halo or OH;
- R7 is C1-3 alkyl substituted with 0-1 R8 and 0-1 R9, —ORb, —NRaRa, —NRaC(═O)Rb, —NRaC(═O)ORb, —NRaC(═O)NRaRa, —NRaS(═O)pRc, —C(═O)Rb, —C(═O)ORb, —C(═O)NRaRa, —C(═O)NRaS(═O)pRc, —OC(═O)Rb, —S(═O)pRc, —S(═O)pNRaRa, C3-6 cycloalkyl, or a 4- to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(═O)p, N and NRd, and substituted with 0-5 Rc;
- R8 is halo, —C(═O)ORb, —C(═O)NHRa, —C(═O)NHORb, or C1-4 alkyl substituted with 0-3 halo or OH;
- R9 is —ORb, —NRaRa, —NRaC(═O)Rb, —NRaC(═O)ORb, —NRaS(═O)pRc, —NRaS(O)pNRaRa, —OC(═O)NRaRa, —OC(═O)NRaORb, —S(═O)pNRaRa, or —S(O)pRc;
- R10 is H, C1-4 alkyl substituted with 0-2 R11, —C(═O)Rb, —C(═O)ORb, —C(═O)NRaRa, C3-6 cycloalkyl substituted with 0-5 Re, or a 4- to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(═O)p, N and NR12, and substituted with 0-5 Re;
- R11 is —OH, —C(═O)OH, or aryl;
- R12 is H, C1-3 alkyl, or aryl;
- Ra is H, C1-6 alkyl substituted with 0-5 Re, C2-6 alkenyl substituted with 0-5 Re, C2-6 alkynyl substituted with 0-5 Re, —(CH2)n—C3-10 carbocyclyl substituted with 0-5 Re, or —(CH2)n-heterocyclyl substituted with 0-5 Re;
- or Ra and Ra together with the nitrogen atom to which they are both attached form a heterocyclyl substituted with 0-5 Re;
- Rb is H, C1-6 alkyl substituted with 0-5 Re, C2-6 alkenyl substituted with 0-5 Re, C2-6 alkynyl substituted with 0-5 Re, —(CH2)n—C3-10carbocyclyl substituted with 0-5 Re, or —(CH2)n-heterocyclyl substituted with 0-5 Re;
- Rc is C1-5 alkyl substituted with 0-5 Re, C2-5 alkenyl substituted with 0-5 Re, C2-5 alkynyl substituted with 0-5 Re, C3-6 carbocyclyl, or heterocyclyl;
- Rd is H or C1-4 alkyl;
- Re is halo, CN, ═O, C1-6 alkyl substituted with 0-5 Rg, C2-6 alkenyl substituted with 0-5 Rg, C2-6 alkynyl substituted with 0-5 Rg, —(CH2)n—C3-6 cycloalkyl, —(CH2)n-aryl, —(CH2)n-heterocyclyl, —(CH2)nORf, or —C(═O)ORf;
- Rf is H or C1-3 alkyl;
- Rg is halo, CN, OH, C1-6 alkyl, C3-6 cycloalkyl, or aryl;
- n is zero, 1, 2, or 3;
- and
- p is zero, 1, or 2.
24 more elements
Dependencies are inferred from the claim text.