This invention is in the area of improved therapeutic methods for difficult to treat locally advanced and/or metastatic cancers in patients whose cancer has advanced while being treated with an immune checkpoint inhibitor due to the development of resistance to the inhibitory effects of the immune checkpoint inhibitor or whose cancer is susceptible to the development of resistance to the effects of an immune checkpoint inhibitor. The methods of the present invention are particularly suitable for a select group of hard-to-treat patients with advanced/metastatic triple negative breast cancer (TNBC), recurrent or metastatic non-small cell lung cancer (NSCLC), advanced or metastatic and unresectable colorectal cancer and locally advanced or metastatic urothelial carcinoma, and provides extended progression free survival (PFS) and/or increased overall survival (OS) in these patient populations.
This invention is in the area of improved combination treatments for a select group of hard- to-treat cancer patients, including, for example, those with advanced/metastatic triple negative breast cancer (TNBC), recurrent or metastatic urothelial cancer (mUC), or a Trop-2 overexpressing cancer such as non-small cell lung cancer (NSCLC), wherein the improved combination includes the use of trilaciclib and sacituzumab govitecan, and provides increased overall survival and/or reduced toxicity.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
This invention is in the area of improved combination treatments for a select group of hard- to-treat cancer patients, including, for example, those with advanced/metastatic triple negative breast cancer (TNBC), recurrent or metastatic urothelial cancer (mUC), or a Trop-2 overexpressing cancer such as non-small cell lung cancer (NSCLC), wherein the improved combination includes the use of trilaciclib and sacituzumab govitecan, and provides increased overall survival and/or reduced toxicity.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
This invention is in the area of improved treatments for a select group of patients with advanced/metastatic triple negative breast cancer (TNBC) which provide increased overall survival. In particular, the improved treatments are for a targeted group of patients receiving first- line treatment for advanced/metastatic TNBC who are checkpoint inhibitor treatment-naïve or, alternatively, in patients with advanced/metastatic TNBC who have prior exposure to an immune checkpoint inhibitor, for example, a programmed cell death protein- 1 (PD-1) and/or programmed death-ligand-1 (PD-L1) inhibitor, in a first-line chemotherapeutic setting and who have developed therapeutic resistance to the immune checkpoint inhibitor leading to disease progression after an initial response.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
This invention is in the area of improved colorectal cancer treatment protocols that provide reduced toxicity compared to currently used regimens, including reduced chemotherapy -induced myelosuppression (CIM), diarrhea, mucositis, and/or stomatitis, while, in some embodiments, also improving anti-cancer efficacy. The improved protocols incorporate a highly selective, transient cyclin dependent kinase (CDK) 4/6 inhibitor into the colorectal cancer treatment protocol, allowing for the expanded use of effective fluorouracil-based multi-agent chemotherapies, for example FOLFOXIRI or FOLFIRINOX, into patient populations previously excluded from these protocols.
An advantageous isolated morphic form of trilaciclib which is 2'-((5-(4- methylpiperazin-1-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'- pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one, for example in the form of a dihydrochloride salt or a dihydrochloride, dihydrate.
This invention is in the area of cell cycle inhibiting compounds for the treatment of disorders involving abnormal cellular proliferation, and include selective CDK2 inhibitors for medical therapy and their pharmaceutically acceptable salts and compositions.
A61P 35/04 - Antineoplastic agents specific for metastasis
C07D 487/12 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains three hetero rings
8.
CYCLIN-DEPENDENT KINASE INHIBITING COMPOUNDS FOR THE TREATMENT OF MEDICAL DISORDERS
This invention is in the area of cell cycle inhibiting compounds for the treatment of disorders involving abnormal cellular proliferation, and include selective CDK2 inhibitors for medical therapy and their pharmaceutically acceptable salts and compositions.
C07D 487/12 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains three hetero rings
C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
A61P 35/04 - Antineoplastic agents specific for metastasis
9.
THERAPEUTIC REGIMENS FOR TREATMENT OF CANCER USING ERIBULIN AND SELECTIVE CDK4/6 INHIBITOR COMBINATIONS
The present invention provides methods and compositions for treating cancers with a combination of eribulin and a selective CDK4/6 inhibitor, wherein the selective CDK4/6 inhibitor reduces eribulin's effects on myelosuppression and/or myeloablation without reducing the efficacy of eribulin therapy.
A61K 31/527 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim spiro-condensed
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 35/04 - Antineoplastic agents specific for metastasis
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Pharmaceutical preparations; pharmaceutical preparations for
use in oncology, improving outcomes from chemotherapy, and
treatment of cancer; therapeutic preparations for use in
patients with cancer. Pharmaceutical research and development; providing medical
and scientific research information in the fields of
oncology, pharmaceuticals, therapies, diseases, and
disorders.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations; pharmaceutical preparations for
use in oncology, improving outcomes from chemotherapy, and
treatment of cancer; therapeutic preparations for use in
patients with cancer.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Pharmaceutical preparations; pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations; pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer.
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Pharmaceutical preparations; pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer. Pharmaceutical research and development; providing medical and scientific research information in the fields of oncology, pharmaceuticals, therapies, diseases, and disorders.
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
(1) Pharmaceutical preparations; pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer (1) Pharmaceutical research and development; providing medical and scientific research information in the fields of oncology, pharmaceuticals, therapies, diseases, and disorders
16.
TARGETED TREATMENT OF CANCERS WITH DYSREGULATED FIBROBLAST GROWTH FACTOR RECEPTOR SIGNALING
The present invention provides advantageous methods and compositions for treating a host having a cancer with dysregulation of the FGFR signaling pathway, which includes administering an effective amount of a selective CDK4/6 inhibitor described herein in combination or alternation with a fibroblast growth factor receptor inhibitor.
The present invention provides advantageous methods and compositions for treating a host having a cancer with dysregulation of the FGFR signaling pathway, which includes administering an effective amount of a selective CDK4/6 inhibitor described herein in combination or alternation with a fibroblast growth factor receptor inhibitor.
36 - Financial, insurance and real estate services
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Health insurance information, namely, providing information regarding prescription drug insurance coverage, prior authorizations, administration of claims procedures, co-pays, and appeals for physicians and patients; financial administration of a patient assistance program for eligible patients to purchase prescription drugs at reduced prices, and providing information related thereto
36 - Financial, insurance and real estate services
Goods & Services
Health insurance information, namely, providing information regarding prescription drug insurance coverage, prior authorizations, administration of claims procedures, co-pays, and appeals for physicians and patients; financial administration of a patient assistance program for eligible patients to purchase prescription drugs at reduced prices, and providing information related thereto
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Pharmaceutical preparations for myeloprotection and anti-tumor effects; pharmaceutical preparations for reducing side effects of chemotherapy; pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer Pharmaceutical research and development; providing medical and scientific research information in the fields of oncology, pharmaceuticals, therapies, diseases, and disorders
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Pharmaceutical preparations for myeloprotection and anti-tumor effects; pharmaceutical preparations for reducing side effects of chemotherapy; pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer Pharmaceutical research and development; providing medical and scientific research information in the fields of oncology, pharmaceuticals, therapies, diseases, and disorders
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for use in oncology, improving outcomes from chemotherapy, and treatment of cancer; therapeutic preparations for use in patients with cancer
24.
PATIENT SELECTION FOR ENHANCEMENT OF ANTI-TUMOR IMMUNITY IN CANCER PATIENTS
A method for increasing the progression free survival or overall survival of a patient with cancer comprising: determining if the cancer has a surrounding microenvironment that is favorable to immune modulation; determining if the chemotherapy regimen induces immunogenic cell death, and if both are yes, administering an effective amount of a CDK 4/6 inhibitor selected from Compounds I, II, III, IV, or V, or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered prior to the administration of the chemotherapy or optionally prior to and concurrently with chemotherapy; and, wherein the increase in progression free survival or overall survival is in comparison to the progression free survival or overall survival based on administration of the chemotherapy alone, either based on literature or otherwise publicly available evidence, a comparative during preclinical or clinical trials, or other means accepted by persons skilled in the field.
A method for increasing the progression free survival or overall survival of a patient with cancer comprising: determining if the cancer has a surrounding microenvironment that is favorable to immune modulation; determining if the chemotherapy regimen induces immunogenic cell death, and if both are yes, administering an effective amount of a CDK 4/6 inhibitor selected from Compounds I, II, III, IV, or V, or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered prior to the administration of the chemotherapy or optionally prior to and concurrently with chemotherapy; and, wherein the increase in progression free survival or overall survival is in comparison to the progression free survival or overall survival based on administration of the chemotherapy alone, either based on literature or otherwise publicly available evidence, a comparative during preclinical or clinical trials, or other means accepted by persons skilled in the field.
This invention is in the area of cell cycle inhibiting compounds for the treatment of disorders involving abnormal cellular proliferation, and include CDK2 and CDK9 inhibitors for medical therapy.
This invention is to methods for treating disorders involving abnormal cellular proliferation that have developed resistance to a selective CDK4/6 inhibitor.
The present invention provides methods and compositions for treating cancers with a combination of eribulin and a selective CDK4/6 inhibitor, wherein the selective CDK4/6 inhibitor reduces eribulin' s effects on myelosuppression and/or myeloablation without reducing the efficacy of eribulin therapy.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
29.
IMPROVED SYNTHESIS OF 1,4-DIAZASPIRO[5.5]UNDECAN-3-ONE
This invention provides a process for preparing 1,4-diazaspiro[5.5]undecan-3-one and analogues thereof that are useful in the preparation of pharmaceutical compound, including for the treatment of disorders involving abnormal cellular proliferation. Chemical intermediates in the process are also provided.
This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt, N-oxide, isotopic derivative or prodrug thereof or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder. The invention also includes a combination thereof with another active agent such as a CDK inhibitor, including a CDK4/6 inhibitor, to treat a disorder mediated by the estrogen receptor, as described in more detail herein.
This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to cancer that has developed resistance to other CDK4/6 inhibitors.
Methods and compositions are described to treat a cancer having a specific oncogenic driving mutation by administering a CDK4/6 inhibitor in combination with an additional kinase inhibitor, wherein the specific combination provides advantageous or synergistic inhibitory activity, delays acquired resistance to the additional kinase inhibitor, and/or extends the efficacy of the kinase inhibitor.
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
A61K 31/4412 - Non-condensed pyridinesHydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
A G1T38 human oral dosage regime that provides a (mean AUC(0-24),ss (h*ng/mL)) / (dose (mg)) ratio of less than 5 and/or a (mean AUC(0-24),ss (h*ng/mL)) / (Absolute Neutrophil Count (cells/mm3)) ratio on day 22 of closing of not greater than 1.25.
This invention is in the area of heterocyclic-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
A G1T38 human oral dosage regime that provides a (mean AUC(0-24),ss (h*ng/mL)) / (dose (mg)) ratio of less than 5 and/or a (mean AUC(0-24),ss (h*ng/mL)) / (Absolute Neutrophil Count (cells/mm3)) ratio on day 22 of closing of not greater than 1.25.
This invention provides an unexpectedly stable, highly crystalline form of the di-HCl salt of 2'-((5-(4-isopropylpiperazin-l-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1'2':1'5]pyrrolo[2,3-d]pyrimidin]-6'-one for advantageous therapeutic pharmaceutical efficacy and dosage form stability.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
This invention provides an unexpectedly stable, highly crystalline form of the di-HCl salt of 2'-((5-(4-isopropylpiperazin-l-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1'2':1'5]pyrrolo[2,3-d]pyrimidin]-6'-one for advantageous therapeutic pharmaceutical efficacy and dosage form stability.
The present invention provides methods for treating a EGFR-mutant cancer in a patient by administering a selective CDK4/6 inhibitor described herein in combination or alternation with an EGFR-TKI to delay or reverse acquired resistance to previously administered EGFR-TKIs. In addition, methods for treating a EGFR-mutant cancer in a patient by administering a selective CDK4/6 inhibitor described herein in combination or alternation with an EGFR-TKI are provided wherein an intrinsically EGFR-TKI resistant EGFR-mutant cancer is sensitized to the effects of the EGFR-TKI.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS (USA)
Inventor
Strum, Jay C.
Thatcher, Gregory R.
Xiong, Rui
Zhao, Jiong
Tonetti, Debra A.
Abstract
Compositions, combinations and methods comprising the administration of a CDK4/6 inhibitor of Formula D with a selective estrogen receptor downregulator of Formula A, B or C that are advantageous for the treatment of abnormal cellular proliferation, including a cancer or a tumor.
THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS (USA)
Inventor
Strum, Jay, C.
Thatcher, Gregory, R.
Xiong, Rui
Zhao, Jiong
Tonetti, Debra, A.
Abstract
Compositions, combinations and methods comprising the administration of a CDK4/6 inhibitor of Formula D with a selective estrogen receptor downregulator of Formula A, B or C that are advantageous for the treatment of abnormal cellular proliferation, including a cancer or a tumor.
The addition of a selective, fast-acting, short half-life CDK 4/6 inhibitor in a very specific dosage regimen to the combination of chemotherapy with a checkpoint inhibitor provides superior results in the treatment of a tumor or cancer. The unexpected discovery is that the short pulsatile specifically-timed administration of a selective, fast-acting, short half-life CDK 4/6 inhibitor during administration of the chemotherapy portion of the triple combination therapy has a profound effect on the immune cells in the cancer microenvironment. In an embodiment, the CCDK 4/6 inhibitor is a compound having the following structure: or a pharmaceutically acceptable salt thereof.
The addition of a selective, fast-acting, short half-life CDK 4/6 inhibitor in a very specific dosage regimen to the combination of chemotherapy with a checkpoint inhibitor provides superior results in the treatment of a tumor or cancer. The unexpected discovery is that the short pulsatile specifically-timed administration of a selective, fast-acting, short half-life CDK 4/6 inhibitor during administration of the chemotherapy portion of the triple combination therapy has a profound effect on the immune cells in the cancer microenvironment.
This invention is in the area of synthesizing pyrimidine-based compounds useful in the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
This invention is in the area of synthesizing pyrimidine-based compounds useful in the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07D 239/28 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
49.
CDK4/6 INHIBITOR DOSAGE FORMULATIONS FOR THE PROTECTION OF HEMATOPOIETIC STEM AND PROGENITOR CELLS DURING CHEMOTHERAPY
This invention is in the area of dosage formulations and methods of administering a CDK4/6 inhibitor for the transient protection of healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC), from damage associated with DNA damaging chemotherapeutic agents in subjects undergoing DNA damaging chemotherapeutic therapies for the treatment of proliferative disorders. In one aspect, improved protection of healthy cells is disclosed using a dosage that provides desirable pharmacokinetic and pharmacodynamic characteristics, including AUC, Tmax, Cmax, dosage-corrected AUC, and dosage -corrected Cmax. In another aspect, a method of treating a subject undergoing chemotherapy for the treatment of a CDK 4/6 -replication independent cellular proliferation disorder by administering Compound 1 is provided.
This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.
This invention directed to methods for treating select RB-positive cancers and other Rb- positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with another chemotherapeutic, for example, an additional kinase inhibitor, PD-1 inhibitor, or BCL-2 inhibitor, or combination thereof.
This invention is in the area of tricyclic lactam compounds for and methods of treating selected Rb-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, treatment of select Rb-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as selective cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.
This invention is in the area of tricyclic lactam compounds and methods for protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC), from the damage associated with ionizing radiation (IR) exposure using selective radioprotectants.
This invention is in the area of tricyclic lactam compounds, compositions and methods of protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, protection of healthy cells is disclosed using compounds that act as cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.
This invention is in the area of tricyclic lactam compounds and methods for treating selected cancers and hyperproliferative disorders. The present invention includes the use of an effective amount of a compound described herein, or its pharmaceutically acceptable salt, prodrug, or isotopic variant, optionally in a pharmaceutical composition, to treat a host, typically a human, with a selected cancer, tumor, hyperproliferative condition, or an inflammatory or immune disorder as described further herein.
This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders, wherein the compounds have the formula:
This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.
This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.
This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.
This invention is in the area of improved compounds and methods for transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC), from the damage associated with ionizing radiation (IR) exposure using selective radioprotectants. Ionizing radiation (IR) is an important therapeutic modality to treat a range of cancers and other proliferative disorders such as tumors. Radiation therapy uses high energy radiation to shrink tumors and kill the proliferating cells.
A process for making a lactam compound of the formula (QQQ) is provided wherein the process comprises (i) treating a carboxylic acid of the formula HOOC-CH2-G-NH- LG with an acid and a dehydrating agent, wherein LG is a leaving group such that the amount of strong acid added allows for the desired transformation to take place without the loss of LG before the cyclization and G represents -C- for a 4-membered ring, -C-C-, -C-O-, -O-C- , -N-C-, -C- N- for a 5-membered ring and similar arrangements of C, O, N, for 6, 7 and 8- membered rings where any open valences are H or an organic moiety or where open valences represent a ring bonded to adjacent atoms or the same atom as allowed by valence to form a spiro ring, and (ii) recovering the lactam (QQQ). A compound of the formula (QQQ) or (RRR) is also provided. (see formula QQQ) (see formula RRR)
C07D 205/08 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
C07D 239/22 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
