Abstract: There is a method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient. The method has the step of systemically administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. There is also a method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient by systemically administering a therapeutically effective amount of a THP1 inhibitor from about 1 mg/kg/day to about 50 mg/kg/day.

Abstract: There is provided a daily dosage regimen for treating pulmonary arterial hypertension. The regimen takes the form of two discrete dosage forms. Each dosage form includes an amount of about 600 mg to about 800 mg of (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate. There is also another method for providing a daily dosage regimen. There is also provided several methods for treating pulmonary arterial hypertension. There is provided a method for reducing the level of serotonin biosynthesis by at least 50%. There is also provided a method for achieving an AUC0-tau of ?2530 ng·hr/mL of (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid. There is provided a method of achieving a >50% reduction in urinary 5-HIAA.

Abstract: There is a method of treating or preventing pulmonary arterial hypertension (PAH) or associated pulmonary arterial hypertension (APAH) in a patient. The method has the step of systemically administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. There is also a method of treating or preventing PAH or APAH in a patient by systemically administering a therapeutically effective amount of a THP1 inhibitor from about 1 mg/kg/day to about 50 mg/kg/day. There is a method for treating PAH or APAH in a patient with a single daily dose.

Abstract: There is a method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient. The method has the step of systemically administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. There is also a method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient by systemically administering a therapeutically effective amount of a THP1 inhibitor from about 1 mg/kg/day to about 50 mg/kg/day.

Abstract: There is a crystalline compound of (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate that exhibits an XRPD pattern having a characteristic peak at 19.05±0.20 (° 2?). There is also a pharmaceutical composition containing the compound. There is also a dosage form containing the crystalline compound and one or more pharmaceutically acceptable excipients. There is also a method for crystallizing/recrystallizing the compound. There is also a method for treating or preventing a disease with the compound.

Abstract: There is a method of treating or preventing interstitial lung disease in a patient. The method includes the step of administering to the patient a therapeutically effective amount of the compound of the following formula: or a pharmaceutically acceptable salt thereof.

Abstract: There is a crystalline compound of (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate that exhibits an XRPD pattern having a characteristic peak at 19.05±0.20 (° 2?). There is also a pharmaceutical composition containing the compound. There is also a dosage form containing the crystalline compound and one or more pharmaceutically acceptable excipients. There is also a method for crystallizing/recrystallizing the compound. There is also a method for treating or preventing a disease with the compound.

Abstract: Methods and compositions for treating inflammatory disorders of the lower airways are disclosed herein. In one aspect, a method for treating an inflammatory disorder of lower airways in a human subject in need thereof is disclosed, including administering directly to the lower airways in the human subject an effective amount of anakinra, where the effective amount of anakinra is 0.01 mg to 100 mg per day.

Abstract: The present invention is directed to spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.

Abstract: The present disclosure is directed to intermediates and salts thereof useful for the preparation of spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1). Processes of preparing the intermediates, salts, and TPH inhibitors are also provided.

Abstract: There is a method of treating or preventing sarcoidosis-associated pulmonary hypertension in a patient. The method has the step of administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing.

Abstract: There is a method of treating or preventing interstitial lung disease in a patient. The method includes the step of administering to the patient a therapeutically effective amount of the compound of the following formula: or a pharmaceutically acceptable salt thereof.

Abstract: There is a method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient. The method has the step of systemically administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1?-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing.

Abstract: The present invention is directed to spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.

Abstract: The present disclosure is directed to intermediates and salts thereof useful for the preparation of spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH 1). Processes of preparing the intermediates, salts, and TPH inhibitors are also provided.