IP Library › Granted Patent US 10,966,980
Granted Patent B2
US 10,966,980 · App. 14/822,265 · Granted Apr 6, 2021

Pyrrolo[2,3-d]pyrimidine derivatives

Inventors: Michael L. Vazquez (Billerica, MA); Neelu Kaila (Lexington, MA); Jamison B. Tuttle (Marblehead, MA); Patrick Robert Verhoest (Newton, MA); Matthew R. Reese (Mystic, CT); Karen J. Coffman (Pawcatuck, CT); Tarek Samad (Chestnut Hill, MA); James M. Duerr (Quincy, MA); Simone Sciabola (Cambridge, MA); Mihir D. Parikh (Groton, CT)
Assignee: Pfizer Inc.
A61K31/519A61K31/5377A61K31/5386A61K45/06C07D487/04C07D491/044C07D491/052C07D498/08C07D519/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,966,980
App. No.
14/822,265
Granted
Apr 6, 2021
Kind
B2
Abstract

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing them, and therapeutic uses thereof.

Claims (73)

1. A compound selected from the group consisting of:

[2,2,2-Trifluoro-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}ethanesulfonamide;]

N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-propane-1-sulfonamide;

2-Methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-cyclobutyl}propane-1-sulfonamide;

cis-3-(Cyanomethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclo-butanesulfonamide;

trans-3-(Cyanomethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclo-butanesulfonamide;

[N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-1-oxetan-3-ylmethane-sulfonamide;]

cis-3-(Cyanomethyl)-3-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}cyclobutanesulfonamide;

trans-3-(Cyanomethyl)-3-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}cyclobutanesulfonamide;

3-(1-Hydroxy-1-methylethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}benzenesulfonamide;

N-{(1S,3R)-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclopentyl}propane-1-sulfonamide;

3,3-Difluoro-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclobutane-sulfonamide;

N-(2-Cyanoethyl)-N-methyl-N′-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}sulfamide;

N-{cis-3-[(Butylsulfonyl)methyl]cyclobutyl}-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-Methyl-N-(trans-3-((propylsulfonyl)methyl)cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(cis-3-{[(2-Cyclopropylethyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-[cis-3-({[(3,3-Difluorocyclobutyl)methyl]sulfonyl}-methyl)cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

(1R, 3R)-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfon-yl]cyclopentane-carbonitrile;

(1S, 3S)-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfon-yl]cyclopentane-carbonitrile;

N-(cis-3-{[(3-Chloro-4-fluorophenyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

[(1S,2S)-trans-2-(cyanomethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}cyclopropanesulfonamide;

(1R,2R)-trans-2-(cyanomethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}cyclopropanesulfonamide]

3-Cyano-3-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}azet-idine-1-sulfonamide;

cis-3-Cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclopentanesulfonamide;

trans-3-Cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclopentane-sulfonamide;

1-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)-sulfonyl]azetidine-3-carbonitrile;

cis-3-Cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-cyclobutanesulfonamide;

trans-3-Cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclobutane-sulfonamide;

cis-3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclo-butanecarbonitrile;

trans-3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclo-butanecarbonitrile;

3-Methyl-1-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfon-yl]azetidine-3-carbonitrile;

(1R,5R)-3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)-sulfonyl]-3-azabicyclo[3.1.0]hexane-1-carbonitrile;

cis-3-(Difluoromethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclo-butane-sulfonamide;

trans-3-(Difluoromethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclo-butanesulfonamide;

cis-1-(3-Cyano-1-methylcyclobutyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}methanesulfonamide;

trans-1-(3-Cyano-1-methylcyclobutyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-cyclobutyl}-methanesulfonamide;

cis-3-Fluoro-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclo-butanesulfonamide;

trans-3-Fluoro-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclo-butyl}cyclobutane-sulfonamide;

cis-3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclo-butanecarbonitrile;

trans-3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclo-butanecarbonitrile;

N-Methyl-N-((1S,3S)-3-(((3,3,3-trifluoropropyl)sulfonyl)methyl)cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-Methyl-N-[cis-3-({[3-(trifluoromethyl)pyrrolidin-1-yl]sulfonyl}methyl)cyclobutyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-[cis-3-({[3-(Difluoromethyl)pyrrolidin-1-yl]sulfonyl}methyl)cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(cis-3-{[(3,3-Difluoropyrrolidin-1-yl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclo-pentanecarbonitrile;

N-{cis-3-[(Benzylsulfonyl)methyl]cyclobutyl}-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

1-methyl-3-{[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfon-yl]methyl}cyclobutanecarbonitrile;

N-[cis-3-({[3-(Difluoromethyl)cyclobutyl]sulfonyl}methyl)cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

2-methyl-1-{3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfon-yl]azetidin-1-yl}propan-1-one;

(1R,3R)-3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclo-pentanecarbonitrile;

N-Methyl-N-{cis-3-[(2-oxa-6-azaspiro[3.3]hept-6-ylsulfonyl)methyl]cyclobutyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

(1R,3S)-3-[({cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclo-pentanecarbonitrile;

N-Methyl-N-{cis-3-[(pentan-3-ylsulfonyl)methyl]cyclobutyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(cis-3-{[(3-Methoxypropyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(cis-3-{[(Cyclohexylmethyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(cis-3-{[(3-Fluoropropyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-Methyl-N-(cis-3-{[(3-methylbutyl)sulfonyl]methyl}cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(cis-3-{[(2-Ethylbutyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(cis-3-{[(2-Cyclopentylethyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-Methyl-N-(cis-3-{[(2-methylbutyl)sulfonyl]methyl}cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-(Bicyclo[1.1.1]pent-1-yl)-N-methyl-1-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methanesulfonamide;

N-Methyl-1-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-N-(pentan-2-yl)methanesulfonamide;

N-Butyl-N-methyl-1-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methane-sulfonamide;

N-(2-Methoxyethyl)-N-methyl-1-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methanesulfonamide;

N-Ethyl-N-methyl-1-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methanesulfonamide;

N-Cyclobutyl-N-methyl-1-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}meth-anesulfonamide;

2,5-Anhydro-1,3,4-trideoxy-3-{methyl[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]amino}-L-threo-pentitol;

N-[cis-3-({[(3,3-Difluoro-1-methylcyclobutyl)methyl]sulfonyl}methyl)cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-Methyl-N-(cis-3-{[(4,4,4-trifluorobutyl)sulfonyl]methyl}cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

N-Methyl-N-(cis-3-{[(3,3,3-Trifluoropropyl)sulfonyl]methyl}cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;

or,

a pharmaceutically acceptable salt thereof.

2. A pharmaceutical or a veterinary composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNEE ADDRESS CORRECTION Recorded Mar 20, 2023
From: PFIZER INC.
To: PFIZER INC.
Reel/Frame 063119/0087 →