The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor.

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Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack; angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

The invention provides compounds of Formula (I) and Formula (II)

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pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

The present invention relates to the field of biomedical technology, in particular to a fusion protein Slit2D2(C386S)-HSA and use thereof in the treatment and/or prevention of fibrotic diseases. In the fusion protein, the amino acid residue is mutated on the basis of the Slit2D2 domain, which improves the stability of the fusion protein compared with the native protein. The above fusion protein is obtained by fusing Slit2D2(C386S) with HSA protein, which prolongs the metabolism time of the drug while improving the stability of the drug. The fusion protein provided by the present invention is more effective than the positive control drug in the prevention and treatment of fibrotic diseases, particularly pulmonary fibrosis, and shows good drug-forming properties.

The present invention relates to the field of biomedical technology, in particular to a fusion protein Slit2D2(C386S)-HSA and use thereof in the treatment and/or prevention of fibrotic diseases. In the fusion protein, the amino acid residue is mutated on the basis of the Slit2D2 domain, which improves the stability of the fusion protein compared with the native protein. The above fusion protein is obtained by fusing Slit2D2(C386S) with HSA protein, which prolongs the metabolism time of the drug while improving the stability of the drug. The fusion protein provided by the present invention is more effective than the positive control drug in the prevention and treatment of fibrotic diseases, particularly pulmonary fibrosis, and shows good drug-forming properties.

The present invention relates to variants of porcine granulocyte colony stimulating factor (pG-CSF). The pG-CSF variants are useful in treating preventing or reducing the incidence of bacterial infections in swine. Methods of treating swine are disclosed.

Compounds capable of activating a neuronal heteromeric nicotinic acetylcholine receptor are provided and can be administered in the form of pharmaceutical compositions of the like. Methods for using the compounds for treating, preventing, or ameliorating respiratory depression and overdose induced by an opioid, or other cause of respiratory depression are also provided. Methods of inducing analgesia, anesthesia, or sedation in a subject, while simultaneously treating, preventing, or ameliorating respiratory depression and overdose induced by an opioid, or other cause of respiratory depression are also provided.

Compounds capable of activating a neuronal heteromeric nicotinic acetylcholine receptor are provided and can be administered in the form of pharmaceutical compositions of the like. Methods for using the compounds for treating, preventing, or ameliorating respiratory depression and overdose induced by an opioid, or other cause of respiratory depression are also provided. Methods of inducing analgesia, anesthesia, or sedation in a subject, while simultaneously treating, preventing, or ameliorating respiratory depression and overdose induced by an opioid, or other cause of respiratory depression are also provided.

5-HT receptor agonists are useful in the treatment of a variety of diseases. Provided herein are methods of treating and/or reducing the occurrence of respiratory depression caused by an opioid in a human patient or patient population using a 5-HT receptor agonist, such as, for example, a 5-HT4 agonist (e.g., fenfluramine). Methods of stimulating one or more 5-HT.sub.4 receptors in the brain of a patient undergoing treatment with an opioid, wherein the patient is at risk of respiratory depression, by administering a 5-HT4 agonist (e.g., fenfluramine) to a subject in need thereof are provided. Pharmaceutical compositions for use in practicing the subject methods are also provided.

Disclosed in certain embodiments are methods of treating neurological ventilatory insufficiency comprising administering to patient in need thereof, an effective amount of a compound selected from Formula (I) as disclosed herein.

Disclosed in certain embodiments are methods of treating neurological ventilatory insufficiency comprising administering to patient in need thereof, an effective amount of a compound selected from Formula (I) as disclosed herein.