Ptc Therapeutics, Inc.

F. Hoffmann-la Roche Ag

Hoffmann-la Roche Inc.

Ptc Theranentics. Inc.

Nikolai A Naryshkin

Amal Dakka

Ellen Welch

Marla L Weetall

Hasane Ratni

Gary Mitchell Karp

Jana Narasimhan

Luke Green

Nanjing Zhang

Emmanuel Pinard

Xiaoyan Zhang

Hongyan Qi

Xin Zhao

Matthew G Woll

Soongyu Choi

Tianle Yang

Charles Romfo

Anthony A Turpoff

Sergey Paushkin

Christopher Robert Trotta

Guangming Chen

Chunshi Li

Meenal Patel

Westley J Friesen

Yuki Tomizawa

Liangxian Cao

Anuradha Bhattacharyya

Chang-Sun Lee

Michael Andrew Arnold

Jiashi Wang

Panayiota Trifillis

Jin Zhuo

Song Xiao Huang

Kari Wiedinger

Wencheng Li

Vijayalakshmi Gabbeta

Kerstin Effenberger

Matthew C Pellegrini

Minakshi B Jani

Anuradha Mehta

Matthew C Pelligrini

Nicole Risher

Jin Zhou

Anthony A Yurpoff

Tom Tuan Luong

Anuradha Roy

Charles M Romfo

Song Huang

The present description relates to compounds of formula (I) useful for improving pre-mRNA splicing in a cell. In particular, another aspect described herein relates to substituted pyrrolo[2,3-d]pyrimidine compounds, forms, and pharmaceutical compositions thereof and methods of use for treating or ameliorating familial dysautonomia.

Substituted pyrrolo [2,3-d]pyrimidines for treating familial dysautonomia

The present description relates' to compounds of formula (I) useful for improving pre-mRNA splicing in a cell. In particular, another aspect of the present description relates to substituted thieno[3,2-b]pyridine compounds, forms, and pharmaceutical compositions thereof and methods of use for treating or ameliorating familial dysautonomia.

Thioeno[3,2-b] pyridin-7-amine compounds for treating familial dysautonomia

The present invention provides compounds of formula (I)

Compounds for treating spinal muscular atrophy

Provided herein are compounds of Formula (I): and forms thereof, wherein w, w, w, w, w, wand ware as defined herein, including compositions thereof and uses therewith for treating spinal muscular atrophy.

In one aspect, described herein is an intronic recognition element for splicing modifier (iREMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains an intronic REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises an intronic REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising an intronic REMS, and uses of those artificial gene constructs to modulate protein production. In another aspect, provided herein are methods for altering endogenous genes to comprise an intronic REMS, and the use of a compound described herein to modulate protein produced from such altered endogenous genes.

Methods for modulating RNA splicing

Described herein is an intronic recognition element for splicing modifier (iREMS) that can be recognized by a small molecule splicing modifier compound of Formula (I) provided herein or a form thereof, wherein W, X, A and B are as defined herein. In one aspect, methods for modifying RNA splicing to modulate the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene that contains an intronic REMS is modified utilizing a splicing modifier compound of Formula (I), are described herein. In another aspect, methods for modifying RNA splicing to modulate the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene is modified to comprise an intronic REMS utilizing a splicing modifier compound of Formula (I), are described herein.

Methods for modifying RNA splicing

In one aspect, described herein is a recognition element for splicing modifier (REMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains a REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises a REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising a REMS, and uses of those artificial gene constructs to modulate functional protein production. In another aspect, provided herein are methods for altering endogenous genes to comprise a REMS, and the use of a compound described herein to modulate the functional protein produced from such altered endogenous genes.

The present invention provides compounds of formula (I) 

Provided herein are compounds of Formula (I): 

Described herein are methods for modulating the amount of a gene product and compounds for use in such methods. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product as the result of gene expression and compounds for use in such methods.

Methods for modulating the amount of RNA transcripts

The present invention provides compounds of formula (I) wherein A, B, X, Y, R1 and R2 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments. 

Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy. In a specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN2 into mRNA that is transcribed from the SMN2 gene. In another specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 into mRNA that is transcribed from the SMN1 gene. In yet another embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 and SMN2 into mRNA that is transcribed from the SMN1 and SMN2 genes, respectively.

Growing community of inventors

South Plainfield, NJ, United States of America

Nikolai A Naryshkin