公开(公告)号：US12202807B2

公开(公告)日：2025-01-21

申请号：US17972220

申请日：2022-10-24

Applicant: MannKind Corporation

Inventor： Kelly Sullivan Kraft ,  John J. Freeman ,  Paul Serwinski ,  Vincent Pavia ,  Otto Phanstiel ,  Navneet Kaur

IPC: C07D241/08 ,  C07C67/30 ,  C07C67/39 ,  C07C201/12

Abstract: Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

公开(公告)号：US20240182486A1

公开(公告)日：2024-06-06

申请号：US18425036

申请日：2024-01-29

Applicant: GEN1E LIFESCIENCES INC.

Inventor： ADAM GALAN ,  WENDY LUO ,  RITU LAL

IPC: C07D491/107 ,  A61P31/14 ,  C07D207/12 ,  C07D211/42 ,  C07D211/46 ,  C07D239/30 ,  C07D241/08 ,  C07D265/30 ,  C07D267/10 ,  C07D491/048 ,  C07D498/18

CPC classification number: C07D491/107 ,  A61P31/14 ,  C07D207/12 ,  C07D211/42 ,  C07D211/46 ,  C07D239/30 ,  C07D241/08 ,  C07D265/30 ,  C07D267/10 ,  C07D491/048 ,  C07D498/18

Abstract: Disclosed herein are p38α mitogen-activated protein kinase inhibitors, pharmaceutical compositions thereof, and therapeutic methods of using the p38α mitogen-activated protein kinase inhibitors.

公开(公告)号：US20230181573A1

公开(公告)日：2023-06-15

申请号：US18106948

申请日：2023-02-07

Applicant: MannKind Corporation

Inventor： Marshall L. Grant ,  Grayson W. Stowell ,  Paul Menkin ,  John J. Freeman, JR.

IPC: A61K31/495 ,  A61K9/00 ,  A61K9/16 ,  A61K9/19 ,  A61K9/14 ,  A61K38/28 ,  A61K45/06 ,  A61M15/00 ,  C07D241/08 ,  A61K31/5575 ,  A61K38/19

CPC classification number: A61K31/495 ,  A61K9/0075 ,  A61K9/1617 ,  A61K9/1694 ,  A61K9/19 ,  A61K9/145 ,  A61K38/28 ,  A61K45/06 ,  A61M15/0028 ,  A61M15/0091 ,  C07D241/08 ,  A61K31/5575 ,  A61K38/193 ,  Y10T428/2982 ,  A61K38/00

Abstract: Disclosed herein are diketopiperazine microparticles having a specific surface area of less than about 67 m2/g. The diketopiperazine microparticle can be fumaryl diketopiperazine and can comprise a drug such as insulin.

公开(公告)号：US11440891B2

公开(公告)日：2022-09-13

申请号：US16866056

申请日：2020-05-04

Applicant: MannKind Corp

Inventor： John J. Freeman ,  Adrienne Stamper ,  Melissa Heitmann

IPC: C07D241/08 ,  B01J31/02

Abstract: The disclosed embodiments detail improved methods for the synthesis of diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an amino acid in the presence of a catalyst in an organic solvent. The catalyst is selected from the group comprising sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride, tributyl phosphate, phenyl phosphonic acid and phosphorous pentoxide among others. The solvent is selected from the group comprising: dimethylacetamide, N-methyl-2-pyrrolidone, diglyme, ethyl glyme, proglyme, ethyldiglyme, m-cresol, p-cresol, o-cresol, xylenes, ethylene glycol and phenol among others.

公开(公告)号：US11414424B2

公开(公告)日：2022-08-16

申请号：US16557281

申请日：2019-08-30

Applicant: Cytokinetics, Inc.

Inventor： Chihyuan Chuang ,  Bradley P. Morgan ,  Mark Vanderwal ,  Luke W. Ashcraft ,  Kevin Lau

IPC: C07D487/10 ,  A61P9/04 ,  C07D241/08 ,  C07D241/38 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D403/08 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/08 ,  C07D413/14 ,  C07D417/08 ,  C07D491/107

Abstract: Provided are compounds of Formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2A, R2B, R3, R4, and R5 are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20220213081A1

公开(公告)日：2022-07-07

申请号：US17566915

申请日：2021-12-31

Applicant: California Institute of Technology

Inventor： Brian M. Stoltz ,  Alexander W. Sun ,  Stephan N. Hess ,  Carina I. Jette ,  Irina Geibel ,  Shoshana Bachman ,  Masaki Hayashi ,  Hideki Shimizu ,  Jeremy B. Morgan ,  Shunya Sakurai ,  Zachary P. Sercel

IPC: C07D413/14 ,  C07D207/26 ,  C07D243/08 ,  C07D239/06 ,  C07D507/00 ,  C07D241/08

Abstract: Described here are transition metal-catalyzed enantioselective arylation and vinylation reactions of α-substituted lactams, such as γ-lactams. The use of various electrophiles and ligands are described, and result in the construction of α-quaternary centers in good yields (up to 91% yield) and high enantioselectivities (up to 97% ee).

公开(公告)号：US11292774B2

公开(公告)日：2022-04-05

申请号：US16798690

申请日：2020-02-24

Applicant: MannKind Corporation

Inventor： John J. Stevenson ,  Destardi Moye-Sherman

IPC: C07D241/08 ,  B01J27/16

Abstract: Provided is a method for the synthesis of N-protected 3,6-bis-[4-aminobutyl]-2,5-diketopiperazine including the step of heating a solution of ε-amino protected lysine in the presence of a catalyst selected from the group consisting of sulfuric acid, phosphoric acid, and phosphorus pentoxide.

公开(公告)号：US11214540B2

公开(公告)日：2022-01-04

申请号：US16613697

申请日：2018-05-15

Applicant: COGNITION THERAPEUTICS, INC.

Inventor： Gilbert M. Rishton ,  Gary C. Look ,  Susan M. Catalano

IPC: C07D491/107 ,  C07D205/04 ,  C07D207/08 ,  C07D207/16 ,  C07D211/22 ,  C07D211/46 ,  C07D211/48 ,  C07D241/04 ,  C07D241/08 ,  C07D265/30 ,  C07D401/04 ,  C07D403/06 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D413/14

Abstract: The present disclosure relates to novel compounds, and pharmaceutical compositions thereof, useful for treating for treating neurodegenerative diseases, including Alzheimer's disease and cognitive decline. Methods for inhibiting synapse number decline or membrane trafficking abnormalities associated with exposure of a neuronal cell to Abeta species are also disclosed. Representative members of these compounds include:

公开(公告)号：US20210355135A1

公开(公告)日：2021-11-18

申请号：US17320874

申请日：2021-05-14

Applicant: GEN1E LIFESCIENCES INC.

Inventor： ADAM GALAN ,  WENDY LUO ,  RITU LAL

IPC: C07D491/107 ,  C07D267/10 ,  C07D239/30 ,  C07D265/30 ,  C07D498/18 ,  C07D491/048 ,  C07D211/46 ,  C07D211/42 ,  C07D207/12 ,  C07D241/08 ,  A61P31/14

Abstract: Disclosed herein are p38α mitogen-activated protein kinase inhibitors, pharmaceutical compositions thereof, and therapeutic methods of using the p38α mitogen-activated protein kinase inhibitors.

公开(公告)号：US20210299260A1

公开(公告)日：2021-09-30

申请号：US17342608

申请日：2021-06-09

Applicant: Ariel Scientific Innovations Ltd.

Inventor： Gary GELLERMAN ,  Andrii BAZYLEVICH

IPC: A61K47/54 ,  A61K47/64 ,  A61K45/06 ,  C07D241/08 ,  A61P35/00

Abstract: Provided herein is a class of anti-cancer conjugates designed to cross the blood-brain barrier (BBB) and thereby deliver a methylation agent into cancerous tumor cells, wherein the conjugate comprises a BBB-shuttle moiety that allows the conjugate to cross the BBB, and at least two methylation moieties of the methyltriazene type attached thereto for effecting DNA methylation in the cancerous cells. Also provided are uses of the conjugates in the treatment of brain cancer.