# US 10,370,405 B2 · C-3 novel triterpenone with C-28 amide derivatives as HIV inhibitors

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- Number: US 10,370,405 B2
- Document ID: US10370405B2
- Status: Granted
- Kind: B2
- Application number: 15/558,677
- Filed: 2016-03-12
- Published: 2018-08-23
- Granted: 2019-08-06
- Earliest claimed: 2016-03-12
- Assignees: Hetero Labs Limited
- Applicants: Hetero Labs Limited
- Inventors: Parthasaradhi Reddy Bandi; Rathnakar Reddy Kura; David Krupadanam Gazula Levi; Panduranga Reddy Adulla; Eswara Rao Bammidi; Bhaskar Reddy Kasireddy; Sudhakar Neela; Carl Thomas Wild; David Eugene Martin; Theodore John Nitz
- Web page: https://patentgrep.com/patent/US10370405B2

## CPC

- C07J 63/008: {Expansion of ring D by one atom, e.g. D homo steroids}
- A61P 31/18: for HIV
- C07J: STEROIDS (seco-steroids C07C)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to C-3 novel triterpenone with C-28 amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases (formula 1).

## Claims

### Claim 1

The A compound of the formula (1):
wherein,
R1 is
wherein Rb is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;
R2 is selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxylalkoxy or substituted or unsubstituted amino alkyl;
R3 is selected from substituted or unsubstituted alkyl, substituted or unsubstituted amine, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl;
or R2 and R3 optionally are taken together with the N-atom and C-atom to which they are attached to form substituted or unsubstituted 4-7 membered N-contained heterocyclyl; wherein the substituent is heterocyclyl;
R4 is selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted amine, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl;
W is —CH2—, substituted or unsubstituted alkyl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl;
R5 is selected from hydroxy, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl; wherein the substituent is halo or hydroxyl alkyl;
‘n’ is 1;
a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable solvate thereof, a pharmaceutically acceptable hydrate thereof, a N-oxide thereof, a tautomer thereof, a regioisomer thereof, a stereoisomer thereof, a prodrug thereof or a polymorph thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is

### Claim 3

A compound selected from the group consisting of:
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3a-((S)-2-(5-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-3,3a,4,5, 5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy) carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3aS)-2-(5-(4-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3, 3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3a-((S)-2-(5-(pyridin-3-yl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-3, 3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-[1,3′-bipyrrolidine]-1′-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethyl cyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-2-(((S)-2-(hydroxy methyl)pyrrolidin-1-yl)methyl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-penta methyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclo penta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-2-((3,3-difluoro pyrrolidin-1-yl)methyl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a] chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-2-((4,4-difluoro piperidin-1-yl)methyl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3a-((2-(5-phenyl-1H-imidazol-2-yl)propan-2-yl)carbamoyl)-3,3a,4,5,5a, 5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy) carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-2-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7, 7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-2-((4-fluoropiperidin-1-yl)methyl)pyrrolidine-1-carbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a, 5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy) carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)propan-2-yl)carbamoyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4, 5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-1-isopropyl-5a,5b,8,8,1a-pentamethyl-3a-((2-methyl-1-(pyrrolidin-1-yl)propan-2-yl)carbamoyl)-2-oxo-3,3a,4,5,5a,5b, 6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy) carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3a-((S)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl)-3,3a,4,5,5a,5b, 6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy) carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((4-chlorobenzyl)(2-(di methylamino)ethyl)carbamoyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b, 6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy) carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid and
(1R,3S)-3-((((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((1-hydroxy-2-methyl propan-2-yl)carbamoyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a, 8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid or
pharmaceutically acceptable salts thereof.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable excipient.

### Claim 5 (depends on 4)

The pharmaceutical composition according to claim 4, wherein the pharmaceutically acceptable excipient is a carrier or diluent.

### Claim 6 (depends on 1)

A method of treating HIV in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to claim 1.

### Claim 7 (depends on 4)

A method of treating HIV in a subject in need thereof comprising administering to the subject the pharmaceutical composition according to claim 4 comprising a therapeutically effective amount of the compound.

### Claim 8 (depends on 3)

A pharmaceutical composition comprising a compound according to claim 3 and at least one pharmaceutically acceptable excipient.

### Claim 9 (depends on 3)

A method of treating HIV in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to claim 3.